Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata - PubMed (original) (raw)

doi: 10.1002/prot.24102. Epub 2012 Jun 4.

Seung Joong Kim, Danalyn Manglicmot, Kevin T Bain, Jeremiah Gilmore, Tarun Gheyi, Jeremy Phillips, Ursula Pieper, Javier Fernandez-Martinez, Josef D Franke, Tsutomu Matsui, Hiro Tsuruta, Shane Atwell, Devon A Thompson, J Spencer Emtage, Stephen R Wasserman, Michael P Rout, Andrej Sali, J Michael Sauder, Steven C Almo, Stephen K Burley

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Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata

Parthasarathy Sampathkumar et al. Proteins. 2012 Aug.

Abstract

The nuclear pore complex (NPC), embedded in the nuclear envelope, is a large, dynamic molecular assembly that facilitates exchange of macromolecules between the nucleus and the cytoplasm. The yeast NPC is an eightfold symmetric annular structure composed of ~456 polypeptide chains contributed by ~30 distinct proteins termed nucleoporins. Nup116, identified only in fungi, plays a central role in both protein import and mRNA export through the NPC. Nup116 is a modular protein with N-terminal "FG" repeats containing a Gle2p-binding sequence motif and a NPC targeting domain at its C-terminus. We report the crystal structure of the NPC targeting domain of Candida glabrata Nup116, consisting of residues 882-1034 [CgNup116(882-1034)], at 1.94 Å resolution. The X-ray structure of CgNup116(882-1034) is consistent with the molecular envelope determined in solution by small-angle X-ray scattering. Structural similarities of CgNup116(882-1034) with homologous domains from Saccharomyces cerevisiae Nup116, S. cerevisiae Nup145N, and human Nup98 are discussed.

Copyright © 2012 Wiley Periodicals, Inc.

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Figures

Figure 1

Figure 1

A: Stereoview of the CgNup116(882-1034) monomer. Cartoon of Chain A is shown as a rainbow from blue to red from N- to C-terminus. B: Comparison of the merged experimental SAXS profile (red) of CgNup116(882-1034) with the SAXS profile computed by IMP FoXS (blue) from the complete monomer model of CgNup116(882-1034). Inset shows the SAXS profiles in the Guinier plot, with a Rg fit of 18.38±0.24 Å. Dmax of radial distribution function, P(r), is 60.65 Å. C and D: Comparison of the shapes of CgNup116(882-1034) (represented as a mesh) calculated from the experimental SAXS profile by GASBOR (C) and SASTBX (D).

Figure 2

Figure 2

A: Structure based sequence alignment of the structures of CgNup116(882-1034, PDB Code 3NF5), ScNup116 bound to ScNup82:ScNup159 complex (PDB Code 3PBP), autoproteolytic domain of ScNup145 (PDB Code 3KEP), and autoproteolytic domain of HsNup98 (PDB Code 2Q5X). Secondary structural elements of CgNup116(882-1034) and ScNup116 bound to ScNup82:ScNup159 complex are displayed in green and black, respectively. Residues of ScNup116 contributing to its binary interaction with ScNup82 β-propeller domain are marked with blue star. Sites of autoproteolysis of ScNup145N and HsNup98 are indicated with an orange circle. The Ser residue at the autoproteolytic site of ScNup145N and HsNup98 are replaced by Glu and Ala in proteins used for structure determination, respectively. B: Stereoview of CgNup116(882-1034; green) superposed on the structure of ScNup116 bound to ScNup82:ScNup159 complex (grey). Helix α4 of CgNup116 is structurally equivalent to the helix αB of ScNup116. C: Stereoview of the CgNup116(882-1034; green) superposed on the autoproteolytic domain of ScNup145 (grey). D: Stereoview of the CgNup116(882-1034; green) superposed on the autoproteolytic domain of HsNup98 (grey). Residues preceding the β1-strands are highlighted in magenta and orange for CgNup116(882-1034) and HsNup98, respectively. The N- and C-terminal residues are shown on the cartoons as blue and red spheres, respectively.

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