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Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN

Napetschnig, Johanna and Blobel, Günter and Hoelz, André (2007) Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN. Proceedings of the National Academy of Sciences of the United States of America, 104 (6). pp. 1783-1788. ISSN 0027-8424. PMCID PMC1794303. https://resolver.caltech.edu/CaltechAUTHORS:20200407-103450755

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Abstract

The mammalian nuclear pore complex (NPC) is an ≈120-MDa proteinaceous assembly consisting of ≈30 proteins and is the sole gate in the nuclear envelope. The human protooncogene Nup214 was first identified as a target for chromosomal translocation involved in leukemogenesis. Nup214 is located on the cytoplasmic face of the NPC and is implicated in anchoring the cytoplasmic filaments of the NPC and recruiting the RNA helicase Ddx19. Here, we present the crystal structure of the human Nup214 N-terminal domain at 1.65-Å resolution. The structure reveals a seven-bladed β-propeller followed by a 30-residue C-terminal extended peptide segment, which folds back onto the β-propeller and binds to its bottom face. The β-propeller repeats lack any recognizable sequence motif and are distinguished by extensive insertions between the canonical β-strands. We propose a mechanism by which the C-terminal peptide extension is involved in NPC assembly.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.0610828104DOIArticle
https://www.pnas.org/cgi/content/full/0610828104/DC1PublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc1794303/PubMed CentralArticle
ORCID:
AuthorORCID
Hoelz, André0000-0003-1726-0127
Additional Information:© 2007 National Academy of Sciences. Contributed by Günter Blobel, December 6, 2006 (received for review November 22, 2006). We dedicate this paper to Henning Friedrich. We thank the Kazusa DNA Research Institute for reagents, B. Manjasetty (National Synchrotron Light Source) and C. Ralston (Advanced Light Source) for excellent scientific support and help with x-ray measurements; J. Janz for help with ITC measurements; S. Etherton and S. Lawrie for help with editing the manuscript; and K. Hsia, M. Kampmann, I. Melcak, V. Nagy, A. Patke, and P. Stavropoulos for comments on the manuscript. Peptide synthesis was performed by The Rockefeller University Protein Center. This work was supported by a Predoctoral Fellowship from the Women in Science Foundation (to J.N.) and a Grant from the Leukemia and Lymphoma Society (to A.H.). G.B. is an Investigator of the Howard Hughes Medical Institute. Author contributions: J.N. and A.H. designed research; J.N. and A.H. performed research; J.N., G.B., and A.H. analyzed data; and J.N. and A.H. wrote the paper. The authors declare no conflict of interest. Data deposition: The structure factors and atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 2OIT). This article contains supporting information online at www.pnas.org/cgi/content/full/0610828104/DC1.
Funders:
Funding AgencyGrant Number
Women in Science FoundationUNSPECIFIED
Leukemia and Lymphoma SocietyUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:β-propeller; mRNA export; leukemia; Dbp5/Ddx19; nuclear pore complex
Issue or Number:6
PubMed Central ID:PMC1794303
Record Number:CaltechAUTHORS:20200407-103450755
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200407-103450755
Official Citation:Crystal structure of the N-terminal domain of the human protooncogene Nup214/CAN. Johanna Napetschnig, Günter Blobel, André Hoelz. Proceedings of the National Academy of Sciences Feb 2007, 104 (6) 1783-1788; DOI: 10.1073/pnas.0610828104
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102380
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:07 Apr 2020 17:48
Last Modified:07 Apr 2020 17:48

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