Pub Date : 2025-12-09DOI: 10.1038/s41594-025-01728-w
Jianwei Zeng, Yong Fu, Pengge Qian, Wei Huang, Qingwei Niu, Wandy L. Beatty, Alan Brown, L. David Sibley, Rui Zhang
Apicomplexan parasites, responsible for toxoplasmosis, cryptosporidiosis and malaria, invade host cells through a unique gliding motility mechanism powered by actomyosin motors and a dynamic organelle called the conoid. Here, using cryo-electron microscopy, we determined structures of four essential complexes of the Toxoplasma gondii conoid: the preconoidal P2 ring, tubulin-based conoid fibers, and the subpellicular and intraconoidal microtubules. Our analysis identified 40 distinct conoid proteins, several of which are essential for parasite lytic growth, as revealed through genetic disruption studies. Comparative analysis of the tubulin-containing complexes sheds light on their functional specialization by microtubule-associated proteins, while the structure of the preconoidal ring pinpoints the site of actin polymerization and initial translocation, enhancing our mechanistic understanding of gliding motility and, therefore, parasite invasion. Zeng et al. applied single-particle cryo-electron microscopy to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host cell invasion.
{"title":"Atomic models of the Toxoplasma cell invasion machinery","authors":"Jianwei Zeng, Yong Fu, Pengge Qian, Wei Huang, Qingwei Niu, Wandy L. Beatty, Alan Brown, L. David Sibley, Rui Zhang","doi":"10.1038/s41594-025-01728-w","DOIUrl":"10.1038/s41594-025-01728-w","url":null,"abstract":"Apicomplexan parasites, responsible for toxoplasmosis, cryptosporidiosis and malaria, invade host cells through a unique gliding motility mechanism powered by actomyosin motors and a dynamic organelle called the conoid. Here, using cryo-electron microscopy, we determined structures of four essential complexes of the Toxoplasma gondii conoid: the preconoidal P2 ring, tubulin-based conoid fibers, and the subpellicular and intraconoidal microtubules. Our analysis identified 40 distinct conoid proteins, several of which are essential for parasite lytic growth, as revealed through genetic disruption studies. Comparative analysis of the tubulin-containing complexes sheds light on their functional specialization by microtubule-associated proteins, while the structure of the preconoidal ring pinpoints the site of actin polymerization and initial translocation, enhancing our mechanistic understanding of gliding motility and, therefore, parasite invasion. Zeng et al. applied single-particle cryo-electron microscopy to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host cell invasion.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 1","pages":"157-170"},"PeriodicalIF":10.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01728-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145705135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1038/s41594-025-01723-1
Tao Li, Ji Chen, Hao Li, Hong Cao, Sheng-You Huang
Cryo-electron microscopy (cryo-EM) has become the mainstream technique for macromolecular structure determination. However, because of intrinsic resolution heterogeneity, accurate modeling of all-atom structure from cryo-EM maps remains challenging even for maps at near-atomic resolution. Addressing the challenge, we present EMProt, a fully automated method for accurate protein structure determination from cryo-EM maps by efficiently integrating map information and structure prediction with a three-track attention network. EMProt is extensively evaluated on a diverse test set of 177 experimental cryo-EM maps with up to 54 chains in a case at <4-Å resolution, and compared to state-of-the-art methods including DeepMainmast, ModelAngelo, phenix.dock_and_rebuild and AlphaFold3. It is shown that EMProt greatly outperforms the existing methods in recovering the protein structure and building the complete structure. In addition, the built models by EMrot exhibit a high accuracy in model-to-map fit and structure validations. Here the authors present an artificial-intelligence-based automated method for improved protein structure determination from cryo-EM density maps by efficiently integrating map information and structure prediction.
{"title":"EMProt improves structure determination from cryo-EM maps","authors":"Tao Li, Ji Chen, Hao Li, Hong Cao, Sheng-You Huang","doi":"10.1038/s41594-025-01723-1","DOIUrl":"10.1038/s41594-025-01723-1","url":null,"abstract":"Cryo-electron microscopy (cryo-EM) has become the mainstream technique for macromolecular structure determination. However, because of intrinsic resolution heterogeneity, accurate modeling of all-atom structure from cryo-EM maps remains challenging even for maps at near-atomic resolution. Addressing the challenge, we present EMProt, a fully automated method for accurate protein structure determination from cryo-EM maps by efficiently integrating map information and structure prediction with a three-track attention network. EMProt is extensively evaluated on a diverse test set of 177 experimental cryo-EM maps with up to 54 chains in a case at <4-Å resolution, and compared to state-of-the-art methods including DeepMainmast, ModelAngelo, phenix.dock_and_rebuild and AlphaFold3. It is shown that EMProt greatly outperforms the existing methods in recovering the protein structure and building the complete structure. In addition, the built models by EMrot exhibit a high accuracy in model-to-map fit and structure validations. Here the authors present an artificial-intelligence-based automated method for improved protein structure determination from cryo-EM density maps by efficiently integrating map information and structure prediction.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 2","pages":"341-350"},"PeriodicalIF":10.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-07DOI: 10.1038/s41594-025-01734-y
Taylor L. Mighell, Ben Lehner
{"title":"Author Correction: A small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCR","authors":"Taylor L. Mighell, Ben Lehner","doi":"10.1038/s41594-025-01734-y","DOIUrl":"10.1038/s41594-025-01734-y","url":null,"abstract":"","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 12","pages":"2633-2633"},"PeriodicalIF":10.1,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01734-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1038/s41594-025-01724-0
Elizabeth T. Abshire, Lynne E. Maquat
The exon junction complex (EJC) begins to assemble on the spliceosome, which deposits EJCs upstream of most exon–exon junctions during pre-messenger RNA (mRNA) splicing. EJCs acquire additional alternative modules that define heterogeneous EJCs during pre-mRNA processing to mRNA in the nucleus and after mRNA export into the cytoplasm. In this Review, we discuss the mechanisms of EJC formation, the many roles of the EJC in pre-mRNA and mRNA regulation and how these roles are influenced by EJC composition. This Review summarizes the various functions of the exon junction complex in RNA splicing and beyond, to influence gene regulation.
{"title":"Gene regulation through exon junction complex modularity","authors":"Elizabeth T. Abshire, Lynne E. Maquat","doi":"10.1038/s41594-025-01724-0","DOIUrl":"10.1038/s41594-025-01724-0","url":null,"abstract":"The exon junction complex (EJC) begins to assemble on the spliceosome, which deposits EJCs upstream of most exon–exon junctions during pre-messenger RNA (mRNA) splicing. EJCs acquire additional alternative modules that define heterogeneous EJCs during pre-mRNA processing to mRNA in the nucleus and after mRNA export into the cytoplasm. In this Review, we discuss the mechanisms of EJC formation, the many roles of the EJC in pre-mRNA and mRNA regulation and how these roles are influenced by EJC composition. This Review summarizes the various functions of the exon junction complex in RNA splicing and beyond, to influence gene regulation.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 12","pages":"2387-2397"},"PeriodicalIF":10.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1038/s41594-025-01726-y
Joseph B. Bridgers, Andreas Carlström, Dawafuti Sherpa, Mary T. Couvillion, Urška Rovšnik, Jingjing Gao, Bowen Wan, Sichen Shao, Martin Ott, L. Stirling Churchman
Mitochondrial gene expression is essential for oxidative phosphorylation. Mitochondrial-encoded mRNAs are translated by dedicated mitochondrial ribosomes (mitoribosomes), whose regulation remains elusive. In Saccharomyces cerevisiae, nuclear-encoded mitochondrial translational activators (TAs) facilitate transcript-specific translation by a yet unknown mechanism. Here, we investigated the function of TAs containing RNA-binding pentatricopeptide repeats using selective mitoribosome profiling and cryo-electron microscopy (cryo-EM) structural analysis. These analyses show that TAs exhibit strong selectivity for mitoribosomes initiating on their target transcripts. Moreover, TA–mitoribosome footprints indicate that TAs recruit mitoribosomes proximal to the start codon. Two cryo-EM structures of mRNA–TA complexes bound to mitoribosomes stalled in the post-initiation, pre-elongation state revealed the general mechanism of TA action. Specifically, the TAs bind to structural elements in the 5′ untranslated region of the client mRNA and the mRNA channel exit to align the mRNA in the small subunit during initiation. Our findings provide a mechanistic basis for understanding how mitochondria achieve transcript-specific translation initiation without relying on general sequence elements to position mitoribosomes at start codons. Mitochondrial translational activators (TAs) facilitate transcript-specific translation. Using selective ribosome profiling and cryo-electron microscopy, the authors show that TAs bind to the 5′ untranslated region of their target transcript to position mitoribosomes for initiation.
{"title":"Translational activators align mRNAs at the small mitoribosomal subunit for translation initiation","authors":"Joseph B. Bridgers, Andreas Carlström, Dawafuti Sherpa, Mary T. Couvillion, Urška Rovšnik, Jingjing Gao, Bowen Wan, Sichen Shao, Martin Ott, L. Stirling Churchman","doi":"10.1038/s41594-025-01726-y","DOIUrl":"10.1038/s41594-025-01726-y","url":null,"abstract":"Mitochondrial gene expression is essential for oxidative phosphorylation. Mitochondrial-encoded mRNAs are translated by dedicated mitochondrial ribosomes (mitoribosomes), whose regulation remains elusive. In Saccharomyces cerevisiae, nuclear-encoded mitochondrial translational activators (TAs) facilitate transcript-specific translation by a yet unknown mechanism. Here, we investigated the function of TAs containing RNA-binding pentatricopeptide repeats using selective mitoribosome profiling and cryo-electron microscopy (cryo-EM) structural analysis. These analyses show that TAs exhibit strong selectivity for mitoribosomes initiating on their target transcripts. Moreover, TA–mitoribosome footprints indicate that TAs recruit mitoribosomes proximal to the start codon. Two cryo-EM structures of mRNA–TA complexes bound to mitoribosomes stalled in the post-initiation, pre-elongation state revealed the general mechanism of TA action. Specifically, the TAs bind to structural elements in the 5′ untranslated region of the client mRNA and the mRNA channel exit to align the mRNA in the small subunit during initiation. Our findings provide a mechanistic basis for understanding how mitochondria achieve transcript-specific translation initiation without relying on general sequence elements to position mitoribosomes at start codons. Mitochondrial translational activators (TAs) facilitate transcript-specific translation. Using selective ribosome profiling and cryo-electron microscopy, the authors show that TAs bind to the 5′ untranslated region of their target transcript to position mitoribosomes for initiation.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 2","pages":"245-258"},"PeriodicalIF":10.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01726-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1038/s41594-025-01730-2
Ok-Ho Shin, Jun Lu, Jeong-Seop Rhee, Diana R. Tomchick, Zhiping P. Pang, Sonja M. Wojcik, Marcial Camacho-Perez, Nils Brose, Mischa Machius, Josep Rizo, Christian Rosenmund, Thomas C. Südhof
{"title":"Editorial Expression of Concern: Munc13 C2B domain is an activity-dependent Ca2+ regulator of synaptic exocytosis","authors":"Ok-Ho Shin, Jun Lu, Jeong-Seop Rhee, Diana R. Tomchick, Zhiping P. Pang, Sonja M. Wojcik, Marcial Camacho-Perez, Nils Brose, Mischa Machius, Josep Rizo, Christian Rosenmund, Thomas C. Südhof","doi":"10.1038/s41594-025-01730-2","DOIUrl":"10.1038/s41594-025-01730-2","url":null,"abstract":"","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 12","pages":"2634-2634"},"PeriodicalIF":10.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01730-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1038/s41594-025-01703-5
Vita Vidmar, Céline Borde, Lisa Bruno, Nataliya Miropolskaya, Maria Takacs, Claire Batisse, Charlotte Saint-André, Chengjin Zhu, Olivier Espéli, Valérie Lamour, Albert Weixlbaumer
During transcription, RNA polymerase (RNAP) continuously unwinds and rewinds DNA, generating negative and positive supercoils upstream and downstream, respectively. Using single-particle cryo-EM, we elucidated how bacterial RNAP and DNA topoisomerase I (TopoI), which relaxes negative supercoils, operate in close spatial proximity. TopoI binds to relaxed DNA upstream of RNAP, and this involves a conformational switch in the TopoI functional domains. This suggests that TopoI exerts a sensing role before the formation of negative supercoils. On DNA substrates mimicking negatively supercoiled DNA, TopoI threads one strand into the active site for cleavage and binds the complementary strand with an auxiliary domain. Transcriptomic and phenotypic analyses suggest that mutations affecting conformational changes in TopoI impact gene expression and operon polarity in bacteria. In summary, we propose a comprehensive model for DNA relaxation in the proximity of active bacterial transcription. Vidmar et al. use cryo-EM to reveal how bacterial RNA polymerase (RNAP) and topoisomerase I (TopoI) cooperate. TopoI switches conformation, senses DNA supercoils near RNAP and relaxes them. Mutations disrupting this process alter bacterial motility and operon polarity.
{"title":"DNA topoisomerase I acts as supercoiling sensor for bacterial transcription elongation","authors":"Vita Vidmar, Céline Borde, Lisa Bruno, Nataliya Miropolskaya, Maria Takacs, Claire Batisse, Charlotte Saint-André, Chengjin Zhu, Olivier Espéli, Valérie Lamour, Albert Weixlbaumer","doi":"10.1038/s41594-025-01703-5","DOIUrl":"10.1038/s41594-025-01703-5","url":null,"abstract":"During transcription, RNA polymerase (RNAP) continuously unwinds and rewinds DNA, generating negative and positive supercoils upstream and downstream, respectively. Using single-particle cryo-EM, we elucidated how bacterial RNAP and DNA topoisomerase I (TopoI), which relaxes negative supercoils, operate in close spatial proximity. TopoI binds to relaxed DNA upstream of RNAP, and this involves a conformational switch in the TopoI functional domains. This suggests that TopoI exerts a sensing role before the formation of negative supercoils. On DNA substrates mimicking negatively supercoiled DNA, TopoI threads one strand into the active site for cleavage and binds the complementary strand with an auxiliary domain. Transcriptomic and phenotypic analyses suggest that mutations affecting conformational changes in TopoI impact gene expression and operon polarity in bacteria. In summary, we propose a comprehensive model for DNA relaxation in the proximity of active bacterial transcription. Vidmar et al. use cryo-EM to reveal how bacterial RNA polymerase (RNAP) and topoisomerase I (TopoI) cooperate. TopoI switches conformation, senses DNA supercoils near RNAP and relaxes them. Mutations disrupting this process alter bacterial motility and operon polarity.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 1","pages":"134-144"},"PeriodicalIF":10.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1038/s41594-025-01707-1
Yukun Wang, Xizi Chen, Maximilian Kümmecke, John W. Watters, Joel E. Cohen, Yanhui Xu, Shixin Liu
Transcription elongation by RNA polymerase II (Pol II) is an integral step in eukaryotic gene expression. The speed of Pol II is controlled by a multitude of elongation factors, but the exact regulatory mechanisms remain incompletely understood, especially for higher eukaryotes. Here we develop a single-molecule platform to visualize the dynamics of individual mammalian transcription elongation complexes (ECs) reconstituted from purified proteins. This platform allows us to follow the elongation and pausing behavior of EC in real time and unambiguously determine the role of each elongation factor in the kinetic control of Pol II. We find that the mammalian EC harbors multiple speed gears dictated by its associated factors and phosphorylation status. Moreover, the elongation factors are not functionally redundant but act hierarchically and synergistically to achieve optimal elongation activity. We propose that such elaborate kinetic regulation underlies the major speed-changing events during the transcription cycle and enables cells to adapt to a changing environment. By reconstituting and visualizing mammalian transcription elongation at the single-molecule level, Wang et al. dissected the effects of individual elongation factors on the speed of RNA polymerase II, which is found to operate as a multi-gear molecular machine.
{"title":"Kinetic control of mammalian transcription elongation","authors":"Yukun Wang, Xizi Chen, Maximilian Kümmecke, John W. Watters, Joel E. Cohen, Yanhui Xu, Shixin Liu","doi":"10.1038/s41594-025-01707-1","DOIUrl":"10.1038/s41594-025-01707-1","url":null,"abstract":"Transcription elongation by RNA polymerase II (Pol II) is an integral step in eukaryotic gene expression. The speed of Pol II is controlled by a multitude of elongation factors, but the exact regulatory mechanisms remain incompletely understood, especially for higher eukaryotes. Here we develop a single-molecule platform to visualize the dynamics of individual mammalian transcription elongation complexes (ECs) reconstituted from purified proteins. This platform allows us to follow the elongation and pausing behavior of EC in real time and unambiguously determine the role of each elongation factor in the kinetic control of Pol II. We find that the mammalian EC harbors multiple speed gears dictated by its associated factors and phosphorylation status. Moreover, the elongation factors are not functionally redundant but act hierarchically and synergistically to achieve optimal elongation activity. We propose that such elaborate kinetic regulation underlies the major speed-changing events during the transcription cycle and enables cells to adapt to a changing environment. By reconstituting and visualizing mammalian transcription elongation at the single-molecule level, Wang et al. dissected the effects of individual elongation factors on the speed of RNA polymerase II, which is found to operate as a multi-gear molecular machine.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 2","pages":"235-244"},"PeriodicalIF":10.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01707-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1038/s41594-025-01720-4
Cells store excess fat in lipid droplets to avoid lipotoxicity and maintain homeostasis. We identified an autophagy-independent role for the autophagy lipid transfer protein ATG2A in helping direct lipids to growing lipid droplets and promoting recruitment of the enzyme DGAT2. This coordination enhances triglyceride storage, protects the endoplasmic reticulum from lipid overload and limits the misrouting of lipids into other metabolic pathways.
{"title":"ATG2A–DGAT2 cooperation fuels lipid droplet growth","authors":"","doi":"10.1038/s41594-025-01720-4","DOIUrl":"10.1038/s41594-025-01720-4","url":null,"abstract":"Cells store excess fat in lipid droplets to avoid lipotoxicity and maintain homeostasis. We identified an autophagy-independent role for the autophagy lipid transfer protein ATG2A in helping direct lipids to growing lipid droplets and promoting recruitment of the enzyme DGAT2. This coordination enhances triglyceride storage, protects the endoplasmic reticulum from lipid overload and limits the misrouting of lipids into other metabolic pathways.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 12","pages":"2385-2386"},"PeriodicalIF":10.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1038/s41594-025-01716-0
Cristian Rocha-Roa, Paige Chandran Blair, Gurpreet Sidhu, Daniel Álvarez, Michael Davey, Elizabeth Conibear, Stefano Vanni
Bulk lipid transport between organelles has been proposed to involve the partnership between bridge-like lipid transfer proteins (BLTPs) and membrane-embedded lipid scramblases. However, for almost all BLTPs, such physical association has not been fully described and, in most cases, the identity of the scramblases is unknown. Here we identify TMEM170-family proteins as endoplasmic reticulum lipid scramblases that physically interact with BLTP1/Csf1 proteins and we provide a revised model detailing the structure of this protein complex in Caenorhabditis elegans. This finding opens avenues to understand the mechanistic basis of lipid transport at membrane contact sites. Rocha-Roa et al. identify TMEM170 proteins as endoplasmic reticulum lipid scramblases that partner with bridge-like lipid transfer proteins BLTP1/Csf1 proteins to enable bulk lipid transport between organelles.
{"title":"TMEM170 proteins are lipid scramblases associated with bridge-type lipid transporters BLTP1/Csf1","authors":"Cristian Rocha-Roa, Paige Chandran Blair, Gurpreet Sidhu, Daniel Álvarez, Michael Davey, Elizabeth Conibear, Stefano Vanni","doi":"10.1038/s41594-025-01716-0","DOIUrl":"10.1038/s41594-025-01716-0","url":null,"abstract":"Bulk lipid transport between organelles has been proposed to involve the partnership between bridge-like lipid transfer proteins (BLTPs) and membrane-embedded lipid scramblases. However, for almost all BLTPs, such physical association has not been fully described and, in most cases, the identity of the scramblases is unknown. Here we identify TMEM170-family proteins as endoplasmic reticulum lipid scramblases that physically interact with BLTP1/Csf1 proteins and we provide a revised model detailing the structure of this protein complex in Caenorhabditis elegans. This finding opens avenues to understand the mechanistic basis of lipid transport at membrane contact sites. Rocha-Roa et al. identify TMEM170 proteins as endoplasmic reticulum lipid scramblases that partner with bridge-like lipid transfer proteins BLTP1/Csf1 proteins to enable bulk lipid transport between organelles.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"33 2","pages":"215-219"},"PeriodicalIF":10.1,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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