@article{02b81412e0144384a3bf2a8f0c410605,
title = "Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex",
abstract = "The nuclear pore complex, composed of proteins termed nucleoporins (Nups), is responsible for nucleocytoplasmic transport in eukaryotes. Nuclear pore complexes (NPCs) form an annular structure composed of the nuclear ring, cytoplasmic ring, a membrane ring, and two inner rings. Nup192 is a major component of the NPC's inner ring. We report the crystal structure of Saccharomyces cerevisiae Nup192 residues 2-960 [ScNup192(2-960)], which adopts an α-helical fold with three domains (i.e.; D1, D2, and D3). Small angle X-ray scattering and electron microscopy (EM) studies reveal that ScNup192(2-960) could undergo long-range transition between {"}open{"} and {"}closed{"} conformations. We obtained a structural model of full-length ScNup192 based on EM, the structure of ScNup192(2-960), and homology modeling. Evolutionary analyses using the ScNup192(2-960) structure suggest that NPCs and vesicle-coating complexes are descended from a common membrane-coating ancestral complex. We show that suppression of Nup192 expression leads to compromised nuclear transport and hypothesize a role for Nup192 in modulating the permeability of the NPC central channel.",
author = "Parthasarathy Sampathkumar and Kim, {Seung Joong} and Paula Upla and Rice, {William J.} and Jeremy Phillips and Timney, {Benjamin L.} and Ursula Pieper and Bonanno, {Jeffrey B.} and Javier Fernandez-Martinez and Zhanna Hakhverdyan and Ketaren, {Natalia E.} and Tsutomu Matsui and Weiss, {Thomas M.} and Stokes, {David L.} and Sauder, {J. Michael} and Burley, {Stephen K.} and Andrej Sali and Rout, {Michael P.} and Almo, {Steven C.}",
note = "Funding Information: Authors are grateful to the scientists at Eli Lilly & Company, San Diego, CA who contributed towards cloning and expression of ScNup192(2–960) during PSI2. P.S. acknowledge the help of R.P. Kumar (Almo lab), W. Shi (BNL), L.L. Morisco (APS), S.T. Sojitra (APS), and S.R. Wasserman (APS) during crystallographic data collection. Funding for the NYSGXRC and NYSGRC were provided by NIH Grants U54 GM074945 (S.K.B.) and U54 GM094662 (S.C.A.), respectively. Additional funding for this work was provided by NIH grants R01 GM062427 (M.P.R.), R01 GM083960 (A.S.), U54 GM103511 and U01 GM098256 (A.S. and M.P.R.). This publication was in part made possible by the Center for Synchrotron Biosciences grant, P30-EB-009998, from the NIBIB. Use of the BNL was supported by the U.S. Department of Energy (DOE) under Contract Number DE-AC02-98CH10886. Use of the APS, ANL was supported by DOE. Access to the LRL-CAT beam line at the APS was provided by Eli Lilly, which operates the facility. Portions of this research were carried out at the SSRL, SLAC National Accelerator Laboratory operated for DOE by Stanford University. The SSRL SMBP is supported by the DOE Office of Biological and Environmental Research, by the NIH, NCRR, Biomedical Technology Program (P41RR001209), and by the NIGMS (P41GM103393). The investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant number C06 RR017528-01-CEM from the NCRR, NIH. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. ",
year = "2013",
month = apr,
day = "2",
doi = "10.1016/j.str.2013.02.005",
language = "English (US)",
volume = "21",
pages = "560--571",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "4",
}