The valley degree of freedom in atomically thin transition metal dichalcogenides, coupled with valley-contrasting optical selection rules, holds great potential for future electronic and optoelectronic devices. Resonant optical nanostructures emerge as promising tools for controlling this degree of freedom at the nanoscale. However, their impact on the circular polarization of valley-selective emission remains poorly understood. In our study, we explore a hybrid system where valley-specific emission from a molybdenum disulfide monolayer interacts with a resonant plasmonic nanosphere. Contrary to the simple intuition that a centrosymmetric nanoresonator mostly preserves the degree of circular polarization, our cryogenic experiments reveal significant depolarization of the photoluminescence scattered by the nanoparticle. This striking effect presents an ideal platform for studying the mechanisms governing light-matter interactions in such hybrid systems. Our full-wave numerical analysis provides insights into the key physical mechanisms affecting the polarization response, offering a pathway toward designing novel valleytronic devices.
{"title":"Influence of resonant plasmonic nanoparticles on optically accessing the valley degree of freedom in 2D semiconductors","authors":"Tobias Bucher, Zlata Fedorova, Mostafa Abasifard, Rajeshkumar Mupparapu, Matthias J. Wurdack, Emad Najafidehaghani, Ziyang Gan, Heiko Knopf, Antony George, Falk Eilenberger, Thomas Pertsch, Andrey Turchanin, Isabelle Staude","doi":"10.1038/s41467-024-54359-y","DOIUrl":"https://doi.org/10.1038/s41467-024-54359-y","url":null,"abstract":"<p>The valley degree of freedom in atomically thin transition metal dichalcogenides, coupled with valley-contrasting optical selection rules, holds great potential for future electronic and optoelectronic devices. Resonant optical nanostructures emerge as promising tools for controlling this degree of freedom at the nanoscale. However, their impact on the circular polarization of valley-selective emission remains poorly understood. In our study, we explore a hybrid system where valley-specific emission from a molybdenum disulfide monolayer interacts with a resonant plasmonic nanosphere. Contrary to the simple intuition that a centrosymmetric nanoresonator mostly preserves the degree of circular polarization, our cryogenic experiments reveal significant depolarization of the photoluminescence scattered by the nanoparticle. This striking effect presents an ideal platform for studying the mechanisms governing light-matter interactions in such hybrid systems. Our full-wave numerical analysis provides insights into the key physical mechanisms affecting the polarization response, offering a pathway toward designing novel valleytronic devices.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41467-024-53825-x
Sebastiaan van der Poel, Juan Hurtado-Gallego, Matthias Blaschke, Rubén López-Nebreda, Almudena Gallego, Marcel Mayor, Fabian Pauly, Herre S. J. van der Zant, Nicolás Agraït
Quantum interference plays an important role in charge transport through single-molecule junctions, even at room temperature. Of special interest is the measurement of the destructive quantum interference dip itself. Such measurements are especially demanding when performed in a continuous mode of operation. Here, we use mechanical modulation experiments at ambient conditions to reconstruct the destructive quantum interference dip of conductance versus displacement. Simultaneous measurements of the Seebeck coefficient show a sinusoidal response across the dip without sign change. Calculations that include electrode distance and energy alignment variations explain both observations quantitatively, emphasizing the crucial role of thermal fluctuations for measurements under ambient conditions. Our results open the way for establishing a closer link between break-junction experiments and theory in explaining single-molecule transport phenomena, especially when describing sharp features in the transmission.
{"title":"Mechanoelectric sensitivity reveals destructive quantum interference in single-molecule junctions","authors":"Sebastiaan van der Poel, Juan Hurtado-Gallego, Matthias Blaschke, Rubén López-Nebreda, Almudena Gallego, Marcel Mayor, Fabian Pauly, Herre S. J. van der Zant, Nicolás Agraït","doi":"10.1038/s41467-024-53825-x","DOIUrl":"https://doi.org/10.1038/s41467-024-53825-x","url":null,"abstract":"<p>Quantum interference plays an important role in charge transport through single-molecule junctions, even at room temperature. Of special interest is the measurement of the destructive quantum interference dip itself. Such measurements are especially demanding when performed in a continuous mode of operation. Here, we use mechanical modulation experiments at ambient conditions to reconstruct the destructive quantum interference dip of conductance versus displacement. Simultaneous measurements of the Seebeck coefficient show a sinusoidal response across the dip without sign change. Calculations that include electrode distance and energy alignment variations explain both observations quantitatively, emphasizing the crucial role of thermal fluctuations for measurements under ambient conditions. Our results open the way for establishing a closer link between break-junction experiments and theory in explaining single-molecule transport phenomena, especially when describing sharp features in the transmission.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"18 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Respiratory syncytial virus (RSV) poses a significant public health challenge, especially among children. Although palivizumab and nirsevimab, neutralizing antibodies (nAbs) targeting the RSV F protein, have been used for prophylaxis, their limitations underscore the need for more effective alternatives. Herein, we present a potent and broad nAb, named 5B11, which exhibits nanogram level of unbiased neutralizing activities against both RSV-A and -B subgroups. Notably, 5B11 shows a ~20-fold increase in neutralizing efficacy compared to 1129 (the murine precursor of palivizumab) and approximately a 3-fold increase in neutralizing efficacy against B18537 in comparison to nirsevimab. Cryo-electron microscopy analysis reveals 5B11’s mechanism of action by targeting a highly conserved epitope within site V, offering a promising strategy with potentially lower risk of escape mutants. Antiviral testing in a female cotton rat model demonstrated that low-dose (1.5 mg/kg) administration of 5B11 achieved comparable prophylactic efficacy to that achieved by high-dose (15 mg/kg) of 1129. Furthermore, the humanized 5B11 showed a superior in vivo antiviral activity against B18537 infection compared to nirsevimab and palivizumab. Therefore, 5B11 is a promising RSV prophylactic candidate applicable to broad prevention of RSV infection.
{"title":"A potent broad-spectrum neutralizing antibody targeting a conserved region of the prefusion RSV F protein","authors":"Yongpeng Sun, Liqin Liu, Hongsheng Qiang, Hui Sun, Yichao Jiang, Luo Ren, Zemin Jiang, Siyu Lei, Li Chen, Yizhen Wang, Xue Lin, Guosong Wang, Yang Huang, Yuhao Fu, Yujin Shi, Xiuting Chen, Hai Yu, Shaowei Li, Wenxin Luo, Enmei Liu, Qingbing Zheng, Zizheng Zheng, Ningshao Xia","doi":"10.1038/s41467-024-54384-x","DOIUrl":"https://doi.org/10.1038/s41467-024-54384-x","url":null,"abstract":"<p>Respiratory syncytial virus (RSV) poses a significant public health challenge, especially among children. Although palivizumab and nirsevimab, neutralizing antibodies (nAbs) targeting the RSV F protein, have been used for prophylaxis, their limitations underscore the need for more effective alternatives. Herein, we present a potent and broad nAb, named 5B11, which exhibits nanogram level of unbiased neutralizing activities against both RSV-A and -B subgroups. Notably, 5B11 shows a ~20-fold increase in neutralizing efficacy compared to 1129 (the murine precursor of palivizumab) and approximately a 3-fold increase in neutralizing efficacy against B18537 in comparison to nirsevimab. Cryo-electron microscopy analysis reveals 5B11’s mechanism of action by targeting a highly conserved epitope within site V, offering a promising strategy with potentially lower risk of escape mutants. Antiviral testing in a female cotton rat model demonstrated that low-dose (1.5 mg/kg) administration of 5B11 achieved comparable prophylactic efficacy to that achieved by high-dose (15 mg/kg) of 1129. Furthermore, the humanized 5B11 showed a superior in vivo antiviral activity against B18537 infection compared to nirsevimab and palivizumab. Therefore, 5B11 is a promising RSV prophylactic candidate applicable to broad prevention of RSV infection.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"11 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41467-024-54398-5
Anna Höfler, Jun Yu, Jing Yang, Ziguo Zhang, Leifu Chang, Stephen H. McLaughlin, Geoffrey W. Grime, Elspeth F. Garman, Andreas Boland, David Barford
APC/C is a multi-subunit complex that functions as a master regulator of cell division. It controls progression through the cell cycle by timely marking mitotic cyclins and other cell cycle regulatory proteins for degradation. The APC/C itself is regulated by the sequential action of its coactivator subunits CDC20 and CDH1, post-translational modifications, and its inhibitory binding partners EMI1 and the mitotic checkpoint complex. In this study, we took advantage of developments in cryo-electron microscopy to determine the structures of human APC/CCDH1:EMI1 and apo-APC/C at 2.9 Å and 3.2 Å resolution, respectively, providing insights into the regulation of APC/C activity. The high-resolution maps allow the unambiguous assignment of an α-helix to the N-terminus of CDH1 (CDH1α1) in the APC/CCDH1:EMI1 ternary complex. We also identify a zinc-binding module in APC2 that confers structural stability to the complex, and we confirm the presence of zinc ions experimentally. Finally, due to the higher resolution and well defined density of these maps, we are able to build, aided by AlphaFold predictions, several intrinsically disordered regions in different APC/C subunits that likely play a role in proper APC/C assembly and regulation of its activity.
{"title":"Cryo-EM structures of apo-APC/C and APC/CCDH1:EMI1 complexes provide insights into APC/C regulation","authors":"Anna Höfler, Jun Yu, Jing Yang, Ziguo Zhang, Leifu Chang, Stephen H. McLaughlin, Geoffrey W. Grime, Elspeth F. Garman, Andreas Boland, David Barford","doi":"10.1038/s41467-024-54398-5","DOIUrl":"https://doi.org/10.1038/s41467-024-54398-5","url":null,"abstract":"<p>APC/C is a multi-subunit complex that functions as a master regulator of cell division. It controls progression through the cell cycle by timely marking mitotic cyclins and other cell cycle regulatory proteins for degradation. The APC/C itself is regulated by the sequential action of its coactivator subunits CDC20 and CDH1, post-translational modifications, and its inhibitory binding partners EMI1 and the mitotic checkpoint complex. In this study, we took advantage of developments in cryo-electron microscopy to determine the structures of human APC/C<sup>CDH1:EMI1</sup> and apo-APC/C at 2.9 Å and 3.2 Å resolution, respectively, providing insights into the regulation of APC/C activity. The high-resolution maps allow the unambiguous assignment of an α-helix to the N-terminus of CDH1 (CDH1<sup>α1</sup>) in the APC/C<sup>CDH1:EMI1</sup> ternary complex. We also identify a zinc-binding module in APC2 that confers structural stability to the complex, and we confirm the presence of zinc ions experimentally. Finally, due to the higher resolution and well defined density of these maps, we are able to build, aided by AlphaFold predictions, several intrinsically disordered regions in different APC/C subunits that likely play a role in proper APC/C assembly and regulation of its activity.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"252 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41467-024-54413-9
Xufan Li, Samuel Wyss, Emanuil Yanev, Qing-Jie Li, Shuang Wu, Yongwen Sun, Raymond R. Unocic, Joseph Stage, Matthew Strasbourg, Lucas M. Sassi, Yingxin Zhu, Ju Li, Yang Yang, James Hone, Nicholas Borys, P. James Schuck, Avetik R. Harutyunyan
Nanoribbons (NRs) of atomic layer transition metal dichalcogenides (TMDs) can boost the rapidly emerging field of quantum materials owing to their width-dependent phases and electronic properties. However, the controllable downscaling of width by direct growth and the underlying mechanism remain elusive. Here, we demonstrate the vapor-liquid-solid growth of single crystal of single layer NRs of a series of TMDs (MeX2: Me = Mo, W; X = S, Se) under chalcogen vapor atmosphere, seeded by pre-deposited and respective transition metal-alloyed nanoparticles that also control the NR width. We find linear dependence of growth rate on supersaturation, known as a criterion for continues growth mechanism, which decreases with decreasing of NR width driven by the Gibbs-Thomson effect. The NRs show width-dependent photoluminescence and strain-induced quantum emission signatures with up to ≈ 90% purity of single photons. We propose the path and underlying mechanism for width-controllable growth of TMD NRs for applications in quantum optoelectronics.
原子层过渡金属二掺杂物(TMDs)的纳米带(NRs)因其宽度相关的相位和电子特性,可推动量子材料领域的快速发展。然而,通过直接生长实现宽度的可控缩减及其内在机理仍然难以捉摸。在此,我们展示了一系列 TMDs(MeX2:Me = Mo、W;X = S、Se)单层 NR 的气相-液相-固相生长过程。我们发现生长率与过饱和度呈线性关系,过饱和度是继续生长机制的标准,在吉布斯-汤姆森效应的驱动下,过饱和度随 NR 宽度的减小而减小。NR 显示出宽度依赖性光致发光和应变诱导量子发射特征,单光子纯度高达 ≈ 90%。我们提出了 TMD NRs 宽度可控生长的路径和基本机制,以应用于量子光电子学。
{"title":"Width-dependent continuous growth of atomically thin quantum nanoribbons from nanoalloy seeds in chalcogen vapor","authors":"Xufan Li, Samuel Wyss, Emanuil Yanev, Qing-Jie Li, Shuang Wu, Yongwen Sun, Raymond R. Unocic, Joseph Stage, Matthew Strasbourg, Lucas M. Sassi, Yingxin Zhu, Ju Li, Yang Yang, James Hone, Nicholas Borys, P. James Schuck, Avetik R. Harutyunyan","doi":"10.1038/s41467-024-54413-9","DOIUrl":"https://doi.org/10.1038/s41467-024-54413-9","url":null,"abstract":"<p>Nanoribbons (NRs) of atomic layer transition metal dichalcogenides (TMDs) can boost the rapidly emerging field of quantum materials owing to their width-dependent phases and electronic properties. However, the controllable downscaling of width by direct growth and the underlying mechanism remain elusive. Here, we demonstrate the vapor-liquid-solid growth of single crystal of single layer NRs of a series of TMDs (MeX<sub>2</sub>: Me = Mo, W; X = S, Se) under chalcogen vapor atmosphere, seeded by pre-deposited and respective transition metal-alloyed nanoparticles that also control the NR width. We find linear dependence of growth rate on supersaturation, known as a criterion for continues growth mechanism, which decreases with decreasing of NR width driven by the Gibbs-Thomson effect. The NRs show width-dependent photoluminescence and strain-induced quantum emission signatures with up to ≈ 90% purity of single photons. We propose the path and underlying mechanism for width-controllable growth of TMD NRs for applications in quantum optoelectronics.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"57 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41467-024-54473-x
Chuan Peng, Yuling Zhu, Kaibo Zhang, Yiwei Wang, Yi Zheng, Yang Liu, Weili Fu, Hong Tan, Qiang Fu, Mingming Ding
Nonaromatic and nonconjugated fluorescent materials have garnered increasing attention in recent years. However, most non-classical chromophores are derived from electro-rich nitrogen and oxygen atoms, which suffer from short emission wavelengths, low efficiency, limited responsiveness, and obscure luminescence mechanisms. Here we present an emission mechanism in bioactive polycysteine, an aliphatic polymer that displays polymerization- and aggregation-induced emission, high quantum yield, and multicolor emission properties. We show that the hydrogen atoms bonded to the sulfur atoms play a crucial role in luminescence. This enables reversible modulation of polymer fluorescence under reducing and oxidizing conditions, facilitating specific imaging and quantitative detection of redox species in cells and in vivo. Furthermore, the polymer exhibits better anti-inflammatory and antioxidative activities compared to first-line clinical antioxidants, offering a promising platform for in vivo theragnosis of diseases such as osteoarthritis.
{"title":"Redox-switchable multicolor luminescent polymers for theragnosis of osteoarthritis","authors":"Chuan Peng, Yuling Zhu, Kaibo Zhang, Yiwei Wang, Yi Zheng, Yang Liu, Weili Fu, Hong Tan, Qiang Fu, Mingming Ding","doi":"10.1038/s41467-024-54473-x","DOIUrl":"https://doi.org/10.1038/s41467-024-54473-x","url":null,"abstract":"<p>Nonaromatic and nonconjugated fluorescent materials have garnered increasing attention in recent years. However, most non-classical chromophores are derived from electro-rich nitrogen and oxygen atoms, which suffer from short emission wavelengths, low efficiency, limited responsiveness, and obscure luminescence mechanisms. Here we present an emission mechanism in bioactive polycysteine, an aliphatic polymer that displays polymerization- and aggregation-induced emission, high quantum yield, and multicolor emission properties. We show that the hydrogen atoms bonded to the sulfur atoms play a crucial role in luminescence. This enables reversible modulation of polymer fluorescence under reducing and oxidizing conditions, facilitating specific imaging and quantitative detection of redox species in cells and in vivo. Furthermore, the polymer exhibits better anti-inflammatory and antioxidative activities compared to first-line clinical antioxidants, offering a promising platform for in vivo theragnosis of diseases such as osteoarthritis.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"33 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41467-024-54509-2
Jake Colautti, Huagang Tan, Nathan P. Bullen, Stephanie S. Thang, Dirk Hackenberger, Andrew C. Doxey, John C. Whitney
Type VI secretion systems (T6SSs) are macromolecular assemblies that deliver toxic effector proteins between adjacent bacteria. These effectors span a wide range of protein families that all lack canonical signal sequences that would target them for export. Consequently, it remains incompletely understood how conserved structural components of the T6SS apparatus recognize a diverse repertoire of effectors. Here, we characterize a widespread family of adaptor proteins, containing the domain of unknown function DUF4123, that enable the recognition and export of evolutionarily unrelated effectors. By examining two nearly identical paralogs of the conserved T6SS spike protein, VgrG, we demonstrate that each spike protein exports a structurally unique effector. We further show that the recruitment of each effector to its respective spike protein requires a cognate adaptor protein. Protein–protein interaction experiments demonstrate that these adaptor proteins specifically tether an effector to a structurally conserved but sequence divergent helix-turn-helix motif found at the C-terminus of its cognate VgrG. Using structural predictions and mutagenesis analyses, we elucidate the molecular contacts required for these interactions and discover that these adaptor proteins contain a structurally conserved N-terminal lobe that has evolved to bind VgrG helix-turn-helix motifs and a structurally variable C-terminal lobe that recognizes diverse effector families. Overall, our work provides molecular insight into a mechanism by which conserved T6SS components recognize structurally diverse effectors.
VI 型分泌系统(T6SS)是在相邻细菌之间传递毒性效应蛋白的大分子集合体。这些效应蛋白涵盖多种蛋白家族,但都缺乏将其作为输出目标的典型信号序列。因此,人们对 T6SS 装置的保守结构组件如何识别各种效应物仍不甚了解。在这里,我们描述了一个广泛的适配蛋白家族,该家族含有未知功能域 DUF4123,能够识别和输出进化上不相关的效应物。通过研究保守的 T6SS 穗状蛋白 VgrG 的两个几乎相同的旁系亲属,我们证明每个穗状蛋白都能输出结构独特的效应物。我们还进一步证明,每种效应物被招募到各自的尖峰蛋白上都需要一种同源的适配蛋白。蛋白质-蛋白质相互作用实验证明,这些适配蛋白能将效应物特异性地拴在其同源 VgrG C 端结构上保守但序列上有差异的螺旋-翻转-螺旋基团上。通过结构预测和诱变分析,我们阐明了这些相互作用所需的分子接触,并发现这些适配蛋白包含一个结构上保守的 N 端叶,它在进化过程中结合了 VgrG 的螺旋-翻转-螺旋图案,以及一个结构上可变的 C 端叶,它能识别不同的效应物家族。总之,我们的工作从分子角度揭示了保守的 T6SS 成分识别结构多样的效应物的机制。
{"title":"A widespread accessory protein family diversifies the effector repertoire of the type VI secretion system spike","authors":"Jake Colautti, Huagang Tan, Nathan P. Bullen, Stephanie S. Thang, Dirk Hackenberger, Andrew C. Doxey, John C. Whitney","doi":"10.1038/s41467-024-54509-2","DOIUrl":"https://doi.org/10.1038/s41467-024-54509-2","url":null,"abstract":"<p>Type VI secretion systems (T6SSs) are macromolecular assemblies that deliver toxic effector proteins between adjacent bacteria. These effectors span a wide range of protein families that all lack canonical signal sequences that would target them for export. Consequently, it remains incompletely understood how conserved structural components of the T6SS apparatus recognize a diverse repertoire of effectors. Here, we characterize a widespread family of adaptor proteins, containing the domain of unknown function DUF4123, that enable the recognition and export of evolutionarily unrelated effectors. By examining two nearly identical paralogs of the conserved T6SS spike protein, VgrG, we demonstrate that each spike protein exports a structurally unique effector. We further show that the recruitment of each effector to its respective spike protein requires a cognate adaptor protein. Protein–protein interaction experiments demonstrate that these adaptor proteins specifically tether an effector to a structurally conserved but sequence divergent helix-turn-helix motif found at the C-terminus of its cognate VgrG. Using structural predictions and mutagenesis analyses, we elucidate the molecular contacts required for these interactions and discover that these adaptor proteins contain a structurally conserved N-terminal lobe that has evolved to bind VgrG helix-turn-helix motifs and a structurally variable C-terminal lobe that recognizes diverse effector families. Overall, our work provides molecular insight into a mechanism by which conserved T6SS components recognize structurally diverse effectors.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"19 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41467-024-54373-0
Yuzhen Feng, Dominik van Bodegraven, Alan Kádek, Ignacio L. B. Munguira, Laura Soria-Martinez, Sarah Nentwich, Sreedeepa Saha, Florian Chardon, Daniel Kavan, Charlotte Uetrecht, Mario Schelhaas, Wouter H. Roos
High-risk human papillomaviruses (HPVs) cause various cancers. While type-specific prophylactic vaccines are available, additional anti-viral strategies are highly desirable. Initial HPV cell entry involves receptor-switching induced by structural capsid modifications. These modifications are initiated by interactions with cellular heparan sulphates (HS), however, their molecular nature and functional consequences remain elusive. Combining virological assays with hydrogen/deuterium exchange mass spectrometry, and atomic force microscopy, we investigate the effect of capsid-HS binding and structural activation. We show how HS-induced structural activation requires a minimal HS-chain length and simultaneous engagement of several binding sites by a single HS molecule. This engagement introduces a pincer-like force that stabilizes the capsid in a conformation with extended capsomer linkers. It results in capsid enlargement and softening, thereby likely facilitating L1 proteolytic cleavage and subsequent L2-externalization, as needed for cell entry. Our data supports the further devising of prophylactic strategies against HPV infections.
{"title":"Glycan-induced structural activation softens the human papillomavirus capsid for entry through reduction of intercapsomere flexibility","authors":"Yuzhen Feng, Dominik van Bodegraven, Alan Kádek, Ignacio L. B. Munguira, Laura Soria-Martinez, Sarah Nentwich, Sreedeepa Saha, Florian Chardon, Daniel Kavan, Charlotte Uetrecht, Mario Schelhaas, Wouter H. Roos","doi":"10.1038/s41467-024-54373-0","DOIUrl":"https://doi.org/10.1038/s41467-024-54373-0","url":null,"abstract":"<p>High-risk human papillomaviruses (HPVs) cause various cancers. While type-specific prophylactic vaccines are available, additional anti-viral strategies are highly desirable. Initial HPV cell entry involves receptor-switching induced by structural capsid modifications. These modifications are initiated by interactions with cellular heparan sulphates (HS), however, their molecular nature and functional consequences remain elusive. Combining virological assays with hydrogen/deuterium exchange mass spectrometry, and atomic force microscopy, we investigate the effect of capsid-HS binding and structural activation. We show how HS-induced structural activation requires a minimal HS-chain length and simultaneous engagement of several binding sites by a single HS molecule. This engagement introduces a pincer-like force that stabilizes the capsid in a conformation with extended capsomer linkers. It results in capsid enlargement and softening, thereby likely facilitating L1 proteolytic cleavage and subsequent L2-externalization, as needed for cell entry. Our data supports the further devising of prophylactic strategies against HPV infections.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"252 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41467-024-54542-1
A. H. Lee, J. Lee, V. Leung, L. Larson, A. Nurmikko
Transmitting meaningful information into brain circuits by electronic means is a challenge facing brain-computer interfaces. A key goal is to find an approach to inject spatially structured local current stimuli across swaths of sensory areas of the cortex. Here, we introduce a wireless approach to multipoint patterned electrical microstimulation by a spatially distributed epicortically implanted network of silicon microchips to target specific areas of the cortex. Each sub-millimeter-sized microchip harvests energy from an external radio-frequency source and converts this into biphasic current injected focally into tissue by a pair of integrated microwires. The amplitude, period, and repetition rate of injected current from each chip are controlled across the implant network by implementing a pre-scheduled, collision-free bitmap wireless communication protocol featuring sub-millisecond latency. As a proof-of-concept technology demonstration, a network of 30 wireless stimulators was chronically implanted into motor and sensory areas of the cortex in a freely moving rat for three months. We explored the effects of patterned intracortical electrical stimulation on trained animal behavior at average RF powers well below regulatory safety limits.
{"title":"Patterned electrical brain stimulation by a wireless network of implantable microdevices","authors":"A. H. Lee, J. Lee, V. Leung, L. Larson, A. Nurmikko","doi":"10.1038/s41467-024-54542-1","DOIUrl":"https://doi.org/10.1038/s41467-024-54542-1","url":null,"abstract":"<p>Transmitting meaningful information into brain circuits by electronic means is a challenge facing brain-computer interfaces. A key goal is to find an approach to inject spatially structured local current stimuli across swaths of sensory areas of the cortex. Here, we introduce a wireless approach to multipoint patterned electrical microstimulation by a spatially distributed epicortically implanted network of silicon microchips to target specific areas of the cortex. Each sub-millimeter-sized microchip harvests energy from an external radio-frequency source and converts this into biphasic current injected focally into tissue by a pair of integrated microwires. The amplitude, period, and repetition rate of injected current from each chip are controlled across the implant network by implementing a pre-scheduled, collision-free bitmap wireless communication protocol featuring sub-millisecond latency. As a proof-of-concept technology demonstration, a network of 30 wireless stimulators was chronically implanted into motor and sensory areas of the cortex in a freely moving rat for three months. We explored the effects of patterned intracortical electrical stimulation on trained animal behavior at average RF powers well below regulatory safety limits.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"57 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1038/s41467-024-54468-8
He Yan, Zhen Lu, Xiaojuan Du, Zhengtao You, Mingkang Yang, Nianle Li, Xuequan Li, Zailue Ni, Hong Wu, Xiangfeng Wang, Lifeng Zhao, Hao Wang
Autophagy, a crucial mechanism for cellular degradation, is regulated by conserved autophagy-related (ATG) core proteins across species. Impairments in autophagy result in significant developmental and reproductive aberrations in mammals. However, autophagy is thought to be functionally dispensable in Arabidopsis thaliana since most of the ATG mutants lack severe growth and reproductive defects. Here, we challenge this perception by unveiling a role for autophagy in male gametophyte development and fertility in Arabidopsis. A detailed re-assessment of atg5 and atg7 mutants found that reduced autophagy activity in germinated pollen accompanied by partial aberrations in sperm cell biogenesis and pollen tube growth, leading to compromised seed formation. Furthermore, we revealed autophagy modulates the spatial organization of actin filaments via targeted degradation of actin depolymerization factors ADF7 and Profilin2 in pollen grains and tubes through a key receptor, Neighbor of BRCA1 (NBR1). Our findings advance the understanding of the evolutionary conservation and diversification of autophagy in modulating male fertility in plants contrasting to mammals.
{"title":"Autophagy modulates Arabidopsis male gametophyte fertility and controls actin organization","authors":"He Yan, Zhen Lu, Xiaojuan Du, Zhengtao You, Mingkang Yang, Nianle Li, Xuequan Li, Zailue Ni, Hong Wu, Xiangfeng Wang, Lifeng Zhao, Hao Wang","doi":"10.1038/s41467-024-54468-8","DOIUrl":"https://doi.org/10.1038/s41467-024-54468-8","url":null,"abstract":"<p>Autophagy, a crucial mechanism for cellular degradation, is regulated by conserved autophagy-related (ATG) core proteins across species. Impairments in autophagy result in significant developmental and reproductive aberrations in mammals. However, autophagy is thought to be functionally dispensable in <i>Arabidopsis thaliana</i> since most of the ATG mutants lack severe growth and reproductive defects. Here, we challenge this perception by unveiling a role for autophagy in male gametophyte development and fertility in Arabidopsis. A detailed re-assessment of <i>atg5</i> and <i>atg7</i> mutants found that reduced autophagy activity in germinated pollen accompanied by partial aberrations in sperm cell biogenesis and pollen tube growth, leading to compromised seed formation. Furthermore, we revealed autophagy modulates the spatial organization of actin filaments <i>via</i> targeted degradation of actin depolymerization factors ADF7 and Profilin2 in pollen grains and tubes through a key receptor, Neighbor of BRCA1 (NBR1). Our findings advance the understanding of the evolutionary conservation and diversification of autophagy in modulating male fertility in plants contrasting to mammals.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}