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Crystal Structure of the N-Terminal Domain of Nup358/RanBP2

Kassube, Susanne A. and Stuwe, Tobias and Lin, Daniel H. and Antonuk, C. Danielle and Napetschnig, Johanna and Blobel, Günter and Hoelz, André (2012) Crystal Structure of the N-Terminal Domain of Nup358/RanBP2. Journal of Molecular Biology, 423 (5). pp. 752-765. ISSN 0022-2836. PMCID PMC4226657. https://resolver.caltech.edu/CaltechAUTHORS:20121203-105502330

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Abstract

Key steps in mRNA export are the nuclear assembly of messenger ribonucleoprotein particles (mRNPs), the translocation of mRNPs through the nuclear pore complex (NPC), and the mRNP remodeling events at the cytoplasmic side of the NPC. Nup358/RanBP2 is a constituent of the cytoplasmic filaments of the NPC specific to higher eukaryotes and provides a multitude of binding sites for the nucleocytoplasmic transport machinery. Here, we present the crystal structure of the Nup358 N-terminal domain (NTD) at 0.95 Å resolution. The structure reveals an α-helical domain that harbors three central tetratricopeptide repeats (TPRs), flanked on each side by an additional solvating amphipathic α helix. Overall, the NTD adopts an unusual extended conformation that lacks the characteristic peptide-binding groove observed in canonical TPR domains. Strikingly, the vast majority of the NTD surface exhibits an evolutionarily conserved, positive electrostatic potential, and we demonstrate that the NTD possesses the capability to bind single-stranded RNA in solution. Together, these data suggest that the NTD contributes to mRNP remodeling events at the cytoplasmic face of the NPC.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.jmb.2012.08.026DOIArticle
http://www.sciencedirect.com/science/article/pii/S002228361200719XPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226657PubMed CentralArticle
Additional Information:© 2012 Elsevier Ltd. Received 24 July 2012; received in revised form 24 August 2012; accepted 28 August 2012. Available online 7 September 2012. Edited by I. Wilson. We thank Erik Debler, Martin Jinek, and Alina Patke for critical reading of the manuscript; Stephanie Etherton for help with editing of the manuscript; Evelyn Stuwe for help with fluorescence microscopy; David King for mass spectrometry analysis; and the Berger laboratory for use of their spectrometer for fluorescence anisotropy. 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. S.K. was supported by a fellowship of the German National Academic Foundation, J.N. was supported by a fellowship of the Women in Science Foundation, and A.H. was supported by a Specialized Center of Research grant from the Leukemia and Lymphoma Society, 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
German National Academic FoundationUNSPECIFIED
Women in Science Foundation UNSPECIFIED
Leukemia and Lymphoma SocietyUNSPECIFIED
Albert Wyrick V Scholar Award of the V Foundation for Cancer Research UNSPECIFIED
Edward Mallinckrodt Jr. Foundation 54th Mallinckrodt Scholar Award UNSPECIFIED
Sidney Kimmel Foundation for Cancer Research Kimmel Scholar AwardUNSPECIFIED
Subject Keywords:X-ray crystallography; tetratricopeptide repeat (TPR); fluorescence localization microscopy; nuclear pore complex (NPC); RNA binding protein
Issue or Number:5
PubMed Central ID:PMC4226657
Record Number:CaltechAUTHORS:20121203-105502330
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20121203-105502330
Official Citation:Susanne A. Kassube, Tobias Stuwe, Daniel H. Lin, C. Danielle Antonuk, Johanna Napetschnig, Günter Blobel, André Hoelz, Crystal Structure of the N-Terminal Domain of Nup358/RanBP2, Journal of Molecular Biology, Volume 423, Issue 5, 9 November 2012, Pages 752-765, ISSN 0022-2836, 10.1016/j.jmb.2012.08.026. (http://www.sciencedirect.com/science/article/pii/S002228361200719X)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35765
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:03 Dec 2012 19:26
Last Modified:03 Oct 2019 04:31

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