F. Luo, X. Gui, Heng Zhou, Jinge Gu, Yichen Li, Xiangyu Liu, Minglei Zhao, Dan Li, Xueming Li, Cong Liu
Thermostable cross-β structures are characteristic of pathological amyloid fibrils, but these structures cannot explain the reversible nature of fibrils formed by RNA-binding proteins such as fused in sarcoma (FUS), involved in RNA granule assembly. Here, we find that two tandem (S/G)Y(S/G) motifs of the human FUS low-complexity domain (FUS LC) form reversible fibrils in a temperature- and phosphorylation-dependent manner. We named these motifs reversible amyloid cores, or RAC1 and RAC2, and determined their atomic structures in fibrillar forms, using microelectron and X-ray diffraction techniques. The RAC1 structure features an ordered-coil fibril spine rather than the extended β-strand typical of amyloids. Ser42, a phosphorylation site of FUS, is critical in the maintenance of the ordered-coil structure, which explains how phosphorylation controls fibril formation. The RAC2 structure shows a labile fibril spine with a wet interface. These structures illuminate the mechanism of reversible fibril formation and dynamic assembly of RNA granules.
{"title":"Atomic structures of FUS LC domain segments reveal bases for reversible amyloid fibril formation.","authors":"F. Luo, X. Gui, Heng Zhou, Jinge Gu, Yichen Li, Xiangyu Liu, Minglei Zhao, Dan Li, Xueming Li, Cong Liu","doi":"10.2210/PDB5XRR/PDB","DOIUrl":"https://doi.org/10.2210/PDB5XRR/PDB","url":null,"abstract":"Thermostable cross-β structures are characteristic of pathological amyloid fibrils, but these structures cannot explain the reversible nature of fibrils formed by RNA-binding proteins such as fused in sarcoma (FUS), involved in RNA granule assembly. Here, we find that two tandem (S/G)Y(S/G) motifs of the human FUS low-complexity domain (FUS LC) form reversible fibrils in a temperature- and phosphorylation-dependent manner. We named these motifs reversible amyloid cores, or RAC1 and RAC2, and determined their atomic structures in fibrillar forms, using microelectron and X-ray diffraction techniques. The RAC1 structure features an ordered-coil fibril spine rather than the extended β-strand typical of amyloids. Ser42, a phosphorylation site of FUS, is critical in the maintenance of the ordered-coil structure, which explains how phosphorylation controls fibril formation. The RAC2 structure shows a labile fibril spine with a wet interface. These structures illuminate the mechanism of reversible fibril formation and dynamic assembly of RNA granules.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"25 1","pages":"341-346"},"PeriodicalIF":16.8,"publicationDate":"2018-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49353881","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}
M. Gallagher-Jones, C. Glynn, D. Boyer, M. Martynowycz, Evelyn Hernandez, Jennifer Miao, Chih-Te Zee, I. Novikova, Lukasz Goldschmidt, Heather T Mcfarlane, G. Helguera, James E. Evans, M. Sawaya, D. Cascio, D. Eisenberg, T. Gonen, José A. Rodríguez
The atomic structure of the infectious, protease-resistant, β-sheet-rich and fibrillar mammalian prion remains unknown. Through the cryo-EM method MicroED, we reveal the sub-angstrom-resolution structure of a protofibril formed by a wild-type segment from the β2–α2 loop of the bank vole prion protein. The structure of this protofibril reveals a stabilizing network of hydrogen bonds that link polar zippers within a sheet, producing motifs we have named ‘polar clasps’.
{"title":"Sub-ångström cryo-EM structure of a prion protofibril reveals a polar clasp","authors":"M. Gallagher-Jones, C. Glynn, D. Boyer, M. Martynowycz, Evelyn Hernandez, Jennifer Miao, Chih-Te Zee, I. Novikova, Lukasz Goldschmidt, Heather T Mcfarlane, G. Helguera, James E. Evans, M. Sawaya, D. Cascio, D. Eisenberg, T. Gonen, José A. Rodríguez","doi":"10.2210/PDB6AXZ/PDB","DOIUrl":"https://doi.org/10.2210/PDB6AXZ/PDB","url":null,"abstract":"The atomic structure of the infectious, protease-resistant, β-sheet-rich and fibrillar mammalian prion remains unknown. Through the cryo-EM method MicroED, we reveal the sub-angstrom-resolution structure of a protofibril formed by a wild-type segment from the β2–α2 loop of the bank vole prion protein. The structure of this protofibril reveals a stabilizing network of hydrogen bonds that link polar zippers within a sheet, producing motifs we have named ‘polar clasps’.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"25 1","pages":"131-134"},"PeriodicalIF":16.8,"publicationDate":"2018-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45863239","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}
G. Knott, Alexandra East-Seletsky, Joshua C. Cofsky, J. Holton, E. Charles, J. Doudna
{"title":"Guide bound structures of a divergent RNA-targeting A cleaving CRISPR-Cas13a enzyme","authors":"G. Knott, Alexandra East-Seletsky, Joshua C. Cofsky, J. Holton, E. Charles, J. Doudna","doi":"10.2210/PDB5W1I/PDB","DOIUrl":"https://doi.org/10.2210/PDB5W1I/PDB","url":null,"abstract":"","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"1 1","pages":""},"PeriodicalIF":16.8,"publicationDate":"2017-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48346470","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}
N. D. Franceschi, Antti Arjonen, N. Elkhatib, K. Denessiouk, A. Wrobel, T. A. Wilson, J. Pouwels, Guillaume Montagnac, D. Owen, J. Ivaska
We gratefully acknowledge the following funding sources: N.d.F. FinPharma Doctoral Program, Instrumentarium Foundation, Orion Research Foundation, Liv och Halsa foundation, Finsk-Norska Medicinska Stiftelsen and the Magnus Ehrnrooth Foundation; J.I. Academy of Finland CoE, European Research Council Consolidator Grant, the Sigrid Juselius Foundation, The Finnish Heart Foundation and Finnish Cancer Organizations. DJO, AGW and TW are funded by Wellcome Trust fellowship 090909 (DJO).
我们感谢以下资助来源:nd.f FinPharma博士项目、仪器仪器基金会、Orion研究基金会、Liv och Halsa基金会、Finsk-Norska Medicinska Stiftelsen和Magnus Ehrnrooth基金会;芬兰科学院，欧洲研究理事会整合者资助，西格里德·尤西利乌斯基金会，芬兰心脏基金会和芬兰癌症组织。DJO, AGW和TW由惠康信托基金090909 (DJO)资助。
{"title":"Selective Integrin Endocytosis is Driven by Alpha Chain:Ap2 Interactions","authors":"N. D. Franceschi, Antti Arjonen, N. Elkhatib, K. Denessiouk, A. Wrobel, T. A. Wilson, J. Pouwels, Guillaume Montagnac, D. Owen, J. Ivaska","doi":"10.2210/PDB5FPI/PDB","DOIUrl":"https://doi.org/10.2210/PDB5FPI/PDB","url":null,"abstract":"We gratefully acknowledge the following funding sources: N.d.F. FinPharma Doctoral Program, Instrumentarium Foundation, Orion Research Foundation, Liv och Halsa foundation, Finsk-Norska Medicinska Stiftelsen and the Magnus Ehrnrooth Foundation; J.I. Academy of Finland CoE, European Research Council Consolidator Grant, the Sigrid Juselius Foundation, The Finnish Heart Foundation and Finnish Cancer Organizations. DJO, AGW and TW are funded by Wellcome Trust fellowship 090909 (DJO).","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"23 1","pages":"172"},"PeriodicalIF":16.8,"publicationDate":"2016-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68195440","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}
L. Zubcevic, M. Herzik, B. C. Chung, G. Lander, Seok-Yong Lee
{"title":"Cryo-Electron Microscopy of the Trpv2 Ion Channel","authors":"L. Zubcevic, M. Herzik, B. C. Chung, G. Lander, Seok-Yong Lee","doi":"10.2210/PDB5AN8/PDB","DOIUrl":"https://doi.org/10.2210/PDB5AN8/PDB","url":null,"abstract":"","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"23 1","pages":"180"},"PeriodicalIF":16.8,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68195129","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}
{"title":"Crystal Structure of Broadly Neutralizing Antibody CH04, Isolated from Donor CH0219, in Complex with Scaffolded Trimeric HIV-1 Env V1V2 Domain from the Clade AE Strain A244","authors":"J. Gorman, M. Yang, P. Kwong","doi":"10.2210/pdb5esz/pdb","DOIUrl":"https://doi.org/10.2210/pdb5esz/pdb","url":null,"abstract":"","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"1 1","pages":""},"PeriodicalIF":16.8,"publicationDate":"2015-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68195423","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}
H. Wallweber, C. Tam, Y. Franke, M. Starovasnik, P. Lupardus
Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family of non-receptor tyrosine kinases, which are essential for proper signaling in immune responses and development. Here we present a 2.0 angstrom resolution crystal structure of a receptor-binding fragment of human TYK2 encompassing the FERM and SH2 domains in complex with a so-called “box2” containing intracellular peptide motif from the IFNα receptor (IFNAR1). The TYK2–IFNAR1 interface reveals an unexpected receptor-binding mode that mimics a SH2 domain–phosphopeptide interaction, with a glutamate replacing the canonical phosphotyrosine residue. This structure provides the first view to our knowledge of a JAK in complex with its cognate receptor and defines the molecular logic through which JAKs evolved to interact with divergent receptor sequences.
{"title":"Structural basis of IFN receptor recognition by TYK2","authors":"H. Wallweber, C. Tam, Y. Franke, M. Starovasnik, P. Lupardus","doi":"10.2210/pdb4po6/pdb","DOIUrl":"https://doi.org/10.2210/pdb4po6/pdb","url":null,"abstract":"Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family of non-receptor tyrosine kinases, which are essential for proper signaling in immune responses and development. Here we present a 2.0 angstrom resolution crystal structure of a receptor-binding fragment of human TYK2 encompassing the FERM and SH2 domains in complex with a so-called “box2” containing intracellular peptide motif from the IFNα receptor (IFNAR1). The TYK2–IFNAR1 interface reveals an unexpected receptor-binding mode that mimics a SH2 domain–phosphopeptide interaction, with a glutamate replacing the canonical phosphotyrosine residue. This structure provides the first view to our knowledge of a JAK in complex with its cognate receptor and defines the molecular logic through which JAKs evolved to interact with divergent receptor sequences.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"21 1","pages":"443"},"PeriodicalIF":16.8,"publicationDate":"2014-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68194115","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}
Xiaohua Lou, G. Toresson, Cindy Benod, J. Suh, Kevin J Philips, P. Webb, J. Gustafsson
{"title":"Structure of the retinoid X receptor alpha-liver X receptor beta (RXR alpha-LXR beta ) heterodimer on DNA.","authors":"Xiaohua Lou, G. Toresson, Cindy Benod, J. Suh, Kevin J Philips, P. Webb, J. Gustafsson","doi":"10.2210/PDB4NQA/PDB","DOIUrl":"https://doi.org/10.2210/PDB4NQA/PDB","url":null,"abstract":"","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"21 1","pages":"277-281"},"PeriodicalIF":16.8,"publicationDate":"2014-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68193982","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 : 2014-01-01DOI: 10.3835/plantgenome2015.10.0001rh
Inês Chen, M. Hodges, S. Lall
volume 32 number 1 january 2014 nature biotechnology stem cell state10, we are likely witnessing the start of a reporting wave defining conditions for the generation of stable ICM-like human pluripotent stem cells. Given the importance of human pluripotency to the stem-cell field, confirmation of ICM-like pluripotency is essential. Like Higgs’ Boson to the field of particle physics, human ICM-like pluripotency was predicted from considerations of symmetry and conservation, and we are yet to unlock its potential.
{"title":"Research highlights","authors":"Inês Chen, M. Hodges, S. Lall","doi":"10.3835/plantgenome2015.10.0001rh","DOIUrl":"https://doi.org/10.3835/plantgenome2015.10.0001rh","url":null,"abstract":"volume 32 number 1 january 2014 nature biotechnology stem cell state10, we are likely witnessing the start of a reporting wave defining conditions for the generation of stable ICM-like human pluripotent stem cells. Given the importance of human pluripotency to the stem-cell field, confirmation of ICM-like pluripotency is essential. Like Higgs’ Boson to the field of particle physics, human ICM-like pluripotency was predicted from considerations of symmetry and conservation, and we are yet to unlock its potential.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"38 1","pages":"1245-1245"},"PeriodicalIF":16.8,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82721422","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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