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Title: Architecture of a Coat for the Nuclear Pore Membrane

Abstract

The symmetric core of the nuclear pore complex can be considered schematically as a series of concentric cylinders. A peripheral cylinder coating the pore membrane contains the previously characterized, elongated heptamer that harbors Sec13-Nup145C in its middle section. Strikingly, Sec13-Nup145C crystallizes as a hetero-octamer in two space groups. Oligomerization of Sec13-Nup145C was confirmed biochemically. Importantly, the numerous interacting surfaces in the hetero-octamer are evolutionarily highly conserved, further underlining the physiological relevance of the oligomerization. The hetero-octamer forms a slightly curved, yet rigid rod of sufficient length to span the entire height of the proposed membrane-adjacent cylinder. In concordance with the dimensions and symmetry of the nuclear pore complex core, we suggest that the cylinder is constructed of four antiparallel rings, each ring being composed of eight heptamers arranged in a head-to-tail fashion. Our model proposes that the hetero-octamer would vertically traverse and connect the four stacked rings.

Authors:
; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
959563
Report Number(s):
BNL-82549-2009-JA
Journal ID: ISSN 0092-8674; CELLB5; TRN: US201016%%707
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cell; Journal Volume: 131; Journal Issue: 7
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; ARCHITECTURE; COATINGS; DIMENSIONS; MEMBRANES; SPACE GROUPS; SYMMETRY; national synchrotron light source

Citation Formats

Hsia,K., Stavropoulos, P., Blobel, G., and Hoelz, A. Architecture of a Coat for the Nuclear Pore Membrane. United States: N. p., 2007. Web. doi:10.1016/j.cell.2007.11.038.
Hsia,K., Stavropoulos, P., Blobel, G., & Hoelz, A. Architecture of a Coat for the Nuclear Pore Membrane. United States. doi:10.1016/j.cell.2007.11.038.
Hsia,K., Stavropoulos, P., Blobel, G., and Hoelz, A. Mon . "Architecture of a Coat for the Nuclear Pore Membrane". United States. doi:10.1016/j.cell.2007.11.038.
@article{osti_959563,
title = {Architecture of a Coat for the Nuclear Pore Membrane},
author = {Hsia,K. and Stavropoulos, P. and Blobel, G. and Hoelz, A.},
abstractNote = {The symmetric core of the nuclear pore complex can be considered schematically as a series of concentric cylinders. A peripheral cylinder coating the pore membrane contains the previously characterized, elongated heptamer that harbors Sec13-Nup145C in its middle section. Strikingly, Sec13-Nup145C crystallizes as a hetero-octamer in two space groups. Oligomerization of Sec13-Nup145C was confirmed biochemically. Importantly, the numerous interacting surfaces in the hetero-octamer are evolutionarily highly conserved, further underlining the physiological relevance of the oligomerization. The hetero-octamer forms a slightly curved, yet rigid rod of sufficient length to span the entire height of the proposed membrane-adjacent cylinder. In concordance with the dimensions and symmetry of the nuclear pore complex core, we suggest that the cylinder is constructed of four antiparallel rings, each ring being composed of eight heptamers arranged in a head-to-tail fashion. Our model proposes that the hetero-octamer would vertically traverse and connect the four stacked rings.},
doi = {10.1016/j.cell.2007.11.038},
journal = {Cell},
number = 7,
volume = 131,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
  • We recently proposed a cylindrical coat for the nuclear pore membrane in the nuclear pore complex (NPC). This scaffold is generated by multiple copies of seven nucleoporins. Here, we report three crystal structures of the nucleoporin pair Seh1{center_dot}Nup85, which is part of the coat cylinder. The Seh1{center_dot}Nup85 assembly bears resemblance in its shape and dimensions to that of another nucleoporin pair, Sec13{center_dot}Nup145C. Furthermore, the Seh1{center_dot}Nup85 structures reveal a hinge motion that may facilitate conformational changes in the NPC during import of integral membrane proteins and/or during nucleocytoplasmic transport. We propose that Seh1{center_dot}Nup85 and Sec13{center_dot}Nup145C form 16 alternating, vertical rods thatmore » are horizontally linked by the three remaining nucleoporins of the coat cylinder. Shared architectural and mechanistic principles with the COPII coat indicate a common evolutionary origin and support the notion that the NPC coat represents another class of membrane coats.« less
  • Nuclear pore complexes (NPCs) facilitate all nucleocytoplasmic transport. These massive protein assemblies are modular, with a stable structural scaffold supporting more dynamically attached components. The scaffold is made from multiple copies of the heptameric Y complex and the heteromeric Nic96 complex. We previously showed that members of these core subcomplexes specifically share an ACE1 fold with Sec31 of the COPII vesicle coat, and we proposed a lattice model for the NPC based on this commonality. Here we present the crystal structure of the heterotrimeric 134-kDa complex of Nup84-Nup145C-Sec13 of the Y complex. The heterotypic ACE1 interaction of Nup84 and Nup145Cmore » is analogous to the homotypic ACE1 interaction of Sec31 that forms COPII lattice edge elements and is inconsistent with the alternative 'fence-like' NPC model. We construct a molecular model of the Y complex and compare the architectural principles of COPII and NPC lattices.« less
  • Nuclear pore complexes (NPCs) are 4060 MDa protein assemblies embedded in the nuclear envelope of eukaryotic cells. NPCs exclusively mediate all transport between cytoplasm and nucleus. The nucleoporins that build the NPC are arranged in a stable core of module-like subcomplexes with eight-fold rotational symmetry. To gain insight into the intricate assembly of the NPC, we have solved the crystal structure of a protein complex between two nucleoporins, human Nup107 and Nup133. Both proteins form elongated structures that interact tightly via a compact interface in tail-to-tail fashion. Additional experiments using structure-guided mutants show that Nup107 is the critical anchor formore » Nup133 to the NPC, positioning Nup133 at the periphery of the NPC. The significant topological differences between Nup107 and Nup133 suggest that {alpha}-helical nucleoporin domains of the NPC scaffold fall in different classes and fulfill largely nonredundant functions.« less