Molecular Architecture of the Major Membrane Ring Component of the Nuclear Pore Complex

Paula Upla; Seung Joong Kim; Parthasarathy Sampathkumar; Kaushik Dutta; Sean M Cahill; Ilan E Chemmama; Rosemary Williams; Jeffrey B Bonanno; William J Rice; David L Stokes; David Cowburn; Steven C Almo; Andrej Sali; Michael P Rout; Javier Fernandez-Martinez

doi:10.1016/j.str.2017.01.006

Molecular Architecture of the Major Membrane Ring Component of the Nuclear Pore Complex

Structure. 2017 Mar 7;25(3):434-445. doi: 10.1016/j.str.2017.01.006. Epub 2017 Feb 2.

Authors

Affiliations

¹ Skirball Institute and Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA; Laboratory of Cellular and Structural Biology, The Rockefeller University, Box 213, 1230 York Avenue, New York, NY 10065, USA.
² Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, UCSF MC 2552, Byers Hall at Mission Bay, 1700 4th Street, Suite 503B, University of California, San Francisco, San Francisco, CA 94158, USA.
³ Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
⁴ New York Structural Biology Center, New York, NY 10027, USA.
⁵ Laboratory of Cellular and Structural Biology, The Rockefeller University, Box 213, 1230 York Avenue, New York, NY 10065, USA.
⁶ Simons Electron Microscopy Center at New York Structural Biology Center, New York, NY 10027, USA.
⁷ Skirball Institute and Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
⁸ Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, UCSF MC 2552, Byers Hall at Mission Bay, 1700 4th Street, Suite 503B, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: sali@salilab.org.
⁹ Laboratory of Cellular and Structural Biology, The Rockefeller University, Box 213, 1230 York Avenue, New York, NY 10065, USA. Electronic address: rout@rockefeller.edu.
¹⁰ Laboratory of Cellular and Structural Biology, The Rockefeller University, Box 213, 1230 York Avenue, New York, NY 10065, USA. Electronic address: jfernandez@rockefeller.edu.

Abstract

The membrane ring that equatorially circumscribes the nuclear pore complex (NPC) in the perinuclear lumen of the nuclear envelope is composed largely of Pom152 in yeast and its ortholog Nup210 (or Gp210) in vertebrates. Here, we have used a combination of negative-stain electron microscopy, nuclear magnetic resonance, and small-angle X-ray scattering methods to determine an integrative structure of the ∼120 kDa luminal domain of Pom152. Our structural analysis reveals that the luminal domain is formed by a flexible string-of-pearls arrangement of nine repetitive cadherin-like Ig-like domains, indicating an evolutionary connection between NPCs and the cell adhesion machinery. The 16 copies of Pom152 known to be present in the yeast NPC are long enough to form the observed membrane ring, suggesting how interactions between Pom152 molecules help establish and maintain the NPC architecture.

Keywords: Gp210; NMR; Nup210; Pom152; SAXS; cadherin; electron microscopy; integrative structure determination; nuclear pore complex; nucleoporin.

MeSH terms

Cell Adhesion
Membrane Glycoproteins / chemistry*
Membrane Glycoproteins / metabolism
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Nuclear Pore / chemistry*
Protein Domains
Saccharomyces cerevisiae / chemistry
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / metabolism
Scattering, Small Angle
X-Ray Diffraction

Substances

Membrane Glycoproteins
POM152 protein, S cerevisiae
Saccharomyces cerevisiae Proteins

Abstract

MeSH terms

Substances

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