Tom A Rapoport

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. Chen Y, Seepersaud R, Bensing B, Sullam P, Rapoport T. Mechanism of a cytosolic O-glycosyltransferase essential for the synthesis of a bacterial adhesion protein. Proc Natl Acad Sci U S A. 2016;113:E1190-9 pubmed publisher
    ..These results explain how the glycosyltransferase modifies a progressively changing substrate molecule. ..
  2. Blok N, Tan D, Wang R, Penczek P, Baker D, DiMaio F, et al. Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy. Proc Natl Acad Sci U S A. 2015;112:E4017-25 pubmed publisher
  3. Rapoport T, Li L, Park E. Structural and Mechanistic Insights into Protein Translocation. Annu Rev Cell Dev Biol. 2017;33:369-390 pubmed publisher
    ..Structures of auxiliary components of the bacterial translocon, YidC and SecD/F, provide additional insight. Taken together, these recent advances result in mechanistic models of protein translocation. ..
  4. Romano F, Blok N, Rapoport T. Peroxisome protein import recapitulated in Xenopus egg extracts. J Cell Biol. 2019;: pubmed publisher
    ..The conserved cysteine in Pex5 is not essential for import or to clear import sites for subsequent rounds of translocation. This new in vitro assay will be useful for further dissecting the mechanism of peroxisome protein import. ..
  5. Catipovic M, Bauer B, Loparo J, Rapoport T. Protein translocation by the SecA ATPase occurs by a power-stroke mechanism. EMBO J. 2019;38: pubmed publisher
    ..The clamp opens after phosphate release and allows passive sliding of the polypeptide chain through the SecA-SecY complex until the next ATP binding event. This power-stroke mechanism may be used by other ATPases that move polypeptides. ..
  6. Wang N, Rapoport T. Reconstituting the reticular ER network - mechanistic implications and open questions. J Cell Sci. 2019;132: pubmed publisher
    ..Here, we review reconstitution experiments with purified curvature-stabilizing proteins and fusion GTPases, discuss mechanistic implications and point out open questions. ..
  7. Wu X, Cabanos C, Rapoport T. Structure of the post-translational protein translocation machinery of the ER membrane. Nature. 2019;566:136-139 pubmed publisher
    ..Our structure shows how the Sec61 channel is activated for post-translational protein translocation. ..
  8. Bodnar N, Kim K, Ji Z, Wales T, Svetlov V, Nudler E, et al. Structure of the Cdc48 ATPase with its ubiquitin-binding cofactor Ufd1-Npl4. Nat Struct Mol Biol. 2018;25:616-622 pubmed publisher
    ..Our results indicate that Npl4 is unique among Cdc48 cofactors and suggest a mechanism for binding and translocation of polyubiquitinated substrates into the ATPase. ..
  9. Wu X, Rapoport T. Mechanistic insights into ER-associated protein degradation. Curr Opin Cell Biol. 2018;53:22-28 pubmed publisher
    ..Following polyubiquitination, substrates are extracted from the membrane by the Cdc48/p97 ATPase complex and transferred to the proteasome. We discuss the molecular mechanism of these processes and point out remaining open questions. ..

More Information

Publications20

  1. Chen Y, Bensing B, Seepersaud R, Mi W, Liao M, Jeffrey P, et al. Unraveling the sequence of cytosolic reactions in the export of GspB adhesin from Streptococcus gordonii. J Biol Chem. 2018;293:5360-5373 pubmed publisher
  2. Tripathi A, Mandon E, Gilmore R, Rapoport T. Two alternative binding mechanisms connect the protein translocation Sec71-Sec72 complex with heat shock proteins. J Biol Chem. 2017;292:8007-8018 pubmed publisher
    ..Taken together, our results suggest that translocation substrates can be recruited to the Sec71-Sec72 complex either post-translationally through Ssa1 or co-translationally through Ssb1. ..
  3. Li L, Fierer J, Rapoport T, Howarth M. Structural analysis and optimization of the covalent association between SpyCatcher and a peptide Tag. J Mol Biol. 2014;426:309-17 pubmed publisher
    ..Together, these results give insight into split protein β-strand complementation and enhance a distinct approach to ultrastable molecular interaction. ..
  4. Baldridge R, Rapoport T. Autoubiquitination of the Hrd1 Ligase Triggers Protein Retrotranslocation in ERAD. Cell. 2016;166:394-407 pubmed publisher
    ..Ubiquitination of lysines in Hrd1's RING-finger domain is required for substrate retrotranslocation in vitro and for ERAD in vivo. Our results suggest that Hrd1 forms a ubiquitin-gated protein-conducting channel. ..
  5. Hu J, Rapoport T. Fusion of the endoplasmic reticulum by membrane-bound GTPases. Semin Cell Dev Biol. 2016;60:105-111 pubmed publisher
  6. Chen Y, Bauer B, Rapoport T, GUMBART J. Conformational Changes of the Clamp of the Protein Translocation ATPase SecA. J Mol Biol. 2015;427:2348-59 pubmed publisher
    ..Mutational disruption of clamp opening or closure abolishes protein translocation. These results suggest how conformational changes of SecA allow substrate binding and movement during protein translocation. ..
  7. Markgraf D, Klemm R, Junker M, Hannibal Bach H, Ejsing C, Rapoport T. An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER. Cell Rep. 2014;6:44-55 pubmed publisher
    ..Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption. ..
  8. Bodnar N, Rapoport T. Molecular Mechanism of Substrate Processing by the Cdc48 ATPase Complex. Cell. 2017;169:722-735.e9 pubmed publisher
    ..Together, these results lead to a new paradigm for the function of Cdc48 and its mammalian ortholog p97/VCP. ..
  9. Liu T, Bian X, Romano F, Shemesh T, Rapoport T, Hu J. Cis and trans interactions between atlastin molecules during membrane fusion. Proc Natl Acad Sci U S A. 2015;112:E1851-60 pubmed publisher
    ..We propose a comprehensive model for ATL-mediated fusion that takes into account futile tethering and competition between cis and trans interactions. ..
  10. Shemesh T, Klemm R, Romano F, Wang S, VAUGHAN J, Zhuang X, et al. A model for the generation and interconversion of ER morphologies. Proc Natl Acad Sci U S A. 2014;111:E5243-51 pubmed publisher
    ..e., small triangular sheets with concave edges. The model agrees with experimental observations and explains how curvature-stabilizing proteins determine ER morphology. ..
  11. Stein A, Ruggiano A, Carvalho P, Rapoport T. Key steps in ERAD of luminal ER proteins reconstituted with purified components. Cell. 2014;158:1375-1388 pubmed publisher
    ..Cdc48p-dependent membrane extraction of polyubiquitinated proteins can be reproduced with reconstituted proteoliposomes. Our results suggest a model for retrotranslocation in which Hrd1p forms a membrane conduit for misfolded proteins. ..