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Structural and Functional Analysis of the C-Terminal Domain of Nup358/RanBP2

Lin, Daniel H. and Zimmermann, Stephan and Stuwe, Tobias and Stuwe, Evelyn and Hoelz, André (2013) Structural and Functional Analysis of the C-Terminal Domain of Nup358/RanBP2. Journal of Molecular Biology, 425 (8). pp. 1318-1329. ISSN 0022-2836. PMCID PMC4226655. http://resolver.caltech.edu/CaltechAUTHORS:20130523-094020553

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Abstract

The nuclear pore complex is the sole mediator of bidirectional transport between the nucleus and cytoplasm. Nup358 is a metazoan-specific nucleoporin that localizes to the cytoplasmic filaments and provides several binding sites for the mobile nucleocytoplasmic transport machinery. Here we present the crystal structure of the C-terminal domain (CTD) of Nup358 at 1.75 Å resolution. The structure reveals that the CTD adopts a cyclophilin-like fold with a non-canonical active-site configuration. We determined biochemically that the CTD possesses weak peptidyl-prolyl isomerase activity and show that the active-site cavity mediates a weak association with the human immunodeficiency virus-1 capsid protein, supporting its role in viral infection. Overall, the surface is evolutionarily conserved, suggesting that the CTD serves as a protein–protein interaction platform. However, we demonstrate that the CTD is dispensable for nuclear envelope localization of Nup358, suggesting that the CTD does not interact with other nucleoporins.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.jmb.2013.01.021DOIArticle
http://www.sciencedirect.com/science/article/pii/S0022283613000375PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226655PubMed CentralArticle
Other Contributors:
ContributionOther Contributors NameIdentifierPersonID (may be blank)
EditorWilson, I.Wilson-IUNSPECIFIED
Additional Information:© 2013 Elsevier Ltd. Received 6 December 2012; Revised 10 January 2013; Accepted 17 January 2013; Available online 23 January 2013 We thank Alina Patke and the members of the Hoelz laboratory for critical reading of the manuscript, Kuang Shen for helpful discussions regarding kinetics analysis, and David Baltimore and Christopher Hill for providing cDNAs for the HIV-1 gag-pol and human CypA, respectively. We thank Jens Kaiser and the scientific staff of SSRL beamline 12–2 for their support with X-ray diffraction measurements. We acknowledge the Gordon and Betty Moore Foundation for their support of the Molecular Observatory at the California Institute of Technology. The operations at the SSRL are supported by the Department of Energy and by the National Institutes of Health. D.H.L. was supported by a National Research Service Award (T32GM07616) from the National Institute of General Medical Sciences. E.S. was supported by a Boehringer Ingelheim Fonds predoctoral fellowship. A.H. was supported by the Albert Wyrick V Scholar Award of the V Foundation for Cancer Research, the 54th Mallinckrodt Scholar Award of the Edward Mallinckrodt, Jr. Foundation, and a Kimmel Scholar Award of the Sidney Kimmel Foundation for Cancer Research.
Funders:
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
Department of Energy (DOE)UNSPECIFIED
NIHUNSPECIFIED
National Institute of General Medical Sciences (NIGMS)T32GM07616
Boehringer Ingelheim Fonds predoctoral fellowshipUNSPECIFIED
V Foundation for Cancer ResearchUNSPECIFIED
Edward Mallinckrodt, Jr. FoundationUNSPECIFIED
Sidney Kimmel Foundation for Cancer ResearchUNSPECIFIED
Subject Keywords:X-ray crystallography; peptidyl-prolyl isomerase; fluorescence localization microscopy; nuclear pore complex (NPC); human immunodeficiency virus (HIV-1)
PubMed Central ID:PMC4226655
Record Number:CaltechAUTHORS:20130523-094020553
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20130523-094020553
Official Citation:Daniel H. Lin, Stephan Zimmermann, Tobias Stuwe, Evelyn Stuwe, André Hoelz, Structural and Functional Analysis of the C-Terminal Domain of Nup358/RanBP2, Journal of Molecular Biology, Volume 425, Issue 8, 26 April 2013, Pages 1318-1329, ISSN 0022-2836, 10.1016/j.jmb.2013.01.021.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:38654
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:31 May 2013 19:27
Last Modified:24 Jul 2017 21:37

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