Molecular Architecture of the Major Membrane Ring Component of the Nuclear Pore Complex.
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.
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.
Paula
P
Upla
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.
Seung Joong
SJ
Kim
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Parthasarathy
P
Sampathkumar
New York Structural Biology Center, New York, NY 10027, USA.
Kaushik
K
Dutta
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Sean M
SM
Cahill
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.
Ilan E
IE
Chemmama
Laboratory of Cellular and Structural Biology, The Rockefeller University, Box 213, 1230 York Avenue, New York, NY 10065, USA.
Rosemary
R
Williams
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Jeffrey B
JB
Bonanno
Simons Electron Microscopy Center at New York Structural Biology Center, New York, NY 10027, USA.
William J
WJ
Rice
Skirball Institute and Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
David L
DL
Stokes
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
David
D
Cowburn
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Steven C
SC
Almo
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.
Andrej
A
Sali
Laboratory of Cellular and Structural Biology, The Rockefeller University, Box 213, 1230 York Avenue, New York, NY 10065, USA. Electronic address: rout@rockefeller.edu.
Michael P
MP
Rout
Laboratory of Cellular and Structural Biology, The Rockefeller University, Box 213, 1230 York Avenue, New York, NY 10065, USA. Electronic address: jfernandez@rockefeller.edu.
Javier
J
Fernandez-Martinez
D002448:Cell Adhesion; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D022022:Nuclear Pore / Q000737:chemistry*; D000072417:Protein Domains; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
D008562:Membrane Glycoproteins; C086449:POM152 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
Gp210; NMR; Nup210; Pom152; SAXS; cadherin; electron microscopy; integrative structure determination; nuclear pore complex; nucleoporin