Structure, Dynamics, Evolution, and Function of a Major Scaffold Component in the Nuclear Pore Complex

Details

• Alternative Title:
  Structure
• Personal Author:
  Sampathkumar, Parthasarathy ; Kim, Seung Joong ; Upla, Paula ; Rice, William J. ; Phillips, Jeremy ; Timney, Benjamin L. ; Pieper, Ursula ; Bonanno, Jeffrey B. ; Fernandez-Martinez, Javier ; Hakhverdyan, Zhanna ; Ketaren, Natalia E. ; Matsui, Tsutomu ; Weiss, Thomas M. ; Stokes, David L. ; Sauder, J. Michael ; Burley, Stephen K. ; Sali, Andrej ; Rout, Michael P. ; Almo, Steven C.
• Description:
  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.
• Subjects:
  Active Transport, Cell Nucleus Article Crystallization Evolution, Molecular Microscopy, Electron Models, Molecular Nuclear Pore Nuclear Pore Complex Proteins Protein Conformation Saccharomyces Cerevisiae Saccharomyces Cerevisiae Proteins Scattering, Small Angle

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• Source:
  Structure. 2013; 21(4):560-571
• Pubmed ID:
  23499021
• Pubmed Central ID:
  PMC3755625
• Document Type:
  Journal Article
• Funding:
  R01 GM083960/GM/NIGMS NIH HHSUnited States/ ; P41RR001209/RR/NCRR NIH HHSUnited States/ ; U54 GM074945/GM/NIGMS NIH HHSUnited States/ ; P41 RR001209/RR/NCRR NIH HHSUnited States/ ; U54 GM094662/GM/NIGMS NIH HHSUnited States/ ; P41 GM103393/GM/NIGMS NIH HHSUnited States/ ; C06 RR017528-01-CEM/CE/NCIPC CDC HHSUnited States/ ; P30 EB009998/EB/NIBIB NIH HHSUnited States/ ; U54 GM103511/GM/NIGMS NIH HHSUnited States/ ; P41GM103393/GM/NIGMS NIH HHSUnited States/ ; P30-EB-009998/EB/NIBIB NIH HHSUnited States/ ; R01 GM071329/GM/NIGMS NIH HHSUnited States/ ; R01 GM062427/GM/NIGMS NIH HHSUnited States/ ; U01 GM098256/GM/NIGMS NIH HHSUnited States/ ; C06 RR017528/RR/NCRR NIH HHSUnited States/
• Volume:
  21
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:32aae53254afcc0a7d7a4daf10856129657b67612111c0806b25a94af86c3e5a
• Download URL:
  https://stacks.cdc.gov/view/cdc/29719/cdc_29719_DS1.pdf
• File Type:
  [PDF - 3.09 MB ]