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Structure of a trimeric nucleoporin complex reveals alternate oligomerization states

Nagy, Vivien and Hsia, Kuo-Chiang and Debler, Erik W. and Kampmann, Martin and Davenport, Andrew M. and Blobel, Günter and Hoelz, André (2009) Structure of a trimeric nucleoporin complex reveals alternate oligomerization states. Proceedings of the National Academy of Sciences of the United States of America, 106 (42). pp. 17693-17698. ISSN 0027-8424. PMCID PMC2764879. https://resolver.caltech.edu/CaltechAUTHORS:20200407-084155336

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Abstract

The heptameric Nup84 complex constitutes an evolutionarily conserved building block of the nuclear pore complex. Here, we present the crystal structure of the heterotrimeric Sec13·Nup145C·Nup84 complex, the centerpiece of the heptamer, at 3.2-Å resolution. Nup84 forms a U-shaped α-helical solenoid domain, topologically similar to two other members of the heptamer, Nup145C and Nup85. The interaction between Nup84 and Nup145C is mediated via a hydrophobic interface located in the kink regions of the two solenoids that is reinforced by additional interactions of two long Nup84 loops. The Nup84 binding site partially overlaps with the homo-dimerization interface of Nup145C, suggesting competing binding events. Fitting of the elongated Z-shaped heterotrimer into electron microscopy (EM) envelopes of the heptamer indicates that structural changes occur at the Nup145C·Nup84 interface. Docking the crystal structures of all heptamer components into the EM envelope constitutes a major advance toward the completion of the structural characterization of the Nup84 complex.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.0909373106DOIArticle
https://www.pnas.org/content/suppl/2009/10/01/0909373106.DCSupplementalPublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764879PubMed CentralArticle
ORCID:
AuthorORCID
Kampmann, Martin0000-0002-3819-7019
Hoelz, André0000-0003-1726-0127
Additional Information:© 2009 National Academy of Sciences. Contributed by Günter Blobel, August 19, 2009 (received for review July 6, 2009). We thank A. Patke, H.-S. Seo, and T. Strowig for discussions and comments on the manuscript; S. Etherton for help with editing the manuscript; D. King for mass spectrometry analysis; and S. Kuebler (Wyatt Technology) and S. Solmaz for assistance with the multiangle light scattering analysis. Edman sequencing was carried out by J. Fernandez at the Rockefeller University Proteomics Resource Center. Analytical ultracentrifugation and isothermal titration calorimetry were carried out by L. Eisele at the Wadsworth Center Biochemistry Core Facility and by S. Bevers at the Biophysics Core Facility at the University of Colorado Denver, respectively. In addition, we thank M. Becker, R. Sanishvili, and R. Fischetti (APS); J. Dickert, S. Morton, K. Royal, and C. Ralston (ALS); and W. Shi (NSLS), for support during data collection. E.W.D. is the Dale F. and Betty Ann Frey Fellow of the Damon Runyon Cancer Research Foundation (DRG-1977-08). A.H. was supported by a grant from the Leukemia and Lymphoma Society. Author contributions: V.N. and A.H. designed research; V.N., K.-C.H., E.W.D., A.M.D., and A.H. performed research; V.N., K.-C.H., E.W.D., M.K., G.B., and A.H. analyzed data; and V.N., E.W.D., G.B., and A.H. wrote the paper. The authors declare no conflict of interest. Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 3IKO). This article contains supporting information online at www.pnas.org/cgi/content/full/0909373106/DCSupplemental.
Funders:
Funding AgencyGrant Number
Damon Runyon Cancer Research FoundationDRG-1977-08
Leukemia and Lymphoma SocietyUNSPECIFIED
Subject Keywords:electron microscopy docking; nuclear pore complex; protein-protein interaction; X-ray crystallography; binding promiscuity
Issue or Number:42
PubMed Central ID:PMC2764879
Record Number:CaltechAUTHORS:20200407-084155336
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200407-084155336
Official Citation:Structure of a trimeric nucleoporin complex reveals alternate oligomerization states. Vivien Nagy, Kuo-Chiang Hsia, Erik W. Debler, Martin Kampmann, Andrew M. Davenport, Günter Blobel, André Hoelz. Proceedings of the National Academy of Sciences Oct 2009, 106 (42) 17693-17698; DOI: 10.1073/pnas.0909373106
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102372
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:07 Apr 2020 15:53
Last Modified:07 Apr 2020 15:53

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