PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Families in Gene Neighborhoods
June 2015
Signaling: A Platform for Opposing Functions
May 2015
Nuclear Pore Complex: A Flexible Transporter
February 2015
Nuclear Pore Complex: Higher Resolution of Macromolecules
February 2015
Nuclear Pore Complex: Integrative Approach to Probe Nup133
February 2015
Piecing Together the Nuclear Pore Complex
February 2015
iTRAQing the Ubiquitinome
July 2014
CAAX Endoproteases
August 2013
The Immune System: A Strong Competitor
June 2013
The Immune System: Strand Swapping for T-Cell Inhibition
June 2013
PDZ Domains
April 2013
Protein Interaction Networks: Adding Structure to Protein Networks
April 2013
Protein Interaction Networks: Morph to Assemble
April 2013
Protein Interaction Networks: Reading Between the Lines
April 2013
Protein Interaction Networks: When the Sum Is Greater than the Parts
April 2013
Alpha-Catenin Connections
March 2013
Cytochrome Oxidase
November 2012
Bacterial Phosphotransferase System
October 2012
Solute Channels
September 2012
Budding ensemble
August 2012
The machines behind the spindle assembly checkpoint
June 2012
G Protein-Coupled Receptors
May 2012
Revealing the Nuclear Pore Complex
March 2012
Topping off the proteasome
March 2012
Anchoring's the way
February 2012
Reading out regioselectivity
December 2011
An effective and cooperative dimer
November 2011
PDZ domains: sometimes it takes two
November 2011
Raising a glass to GLIC
August 2011
A2A Adenosine Receptor
May 2011
A growing family
February 2011
FERM-ly bound
February 2011
January 2011
Guard cells pick up the SLAC
December 2010
Zinc Transporter ZntB
July 2010
Zinc Transporter ZntB
July 2010
Importance of extension for integrin
June 2010
Spot protein-protein interactions… fast
March 2010
Alg13 Subunit of N-Acetylglucosamine Transferase
February 2010
Urea transporter
February 2010
Two-component signaling
December 2009
ABA receptor...this time for real?
November 2009
Network coverage
November 2009
Get3 into the groove
October 2009
Guanine Nucleotide Exchange Factor Vav1 and Rho GTPase Rac1
October 2009
GPCR subunits: Separate but not equal
September 2009
Proofreading RNA
July 2009
Ribonuclease and Ribonuclease Inhibitor
April 2009
The elusive helicase
April 2009
Click for cancer-protein interactions
December 2008

Research Themes Protein-protein interactions

Nuclear Pore Complex: Integrative Approach to Probe Nup133

SBKB [doi:10.1038/sbkb.2014.242]
Featured Article - February 2015
Short description: The integration of three structural methods offers insight into membrane association of the NPC.

Integrative modeling of ScNup133 reveals the population weight averages of four states, a major extended conformation and three minor compact conformations. Figure from ref. 1 , © 2014 The American Society for Biochemistry and Molecular Biology.

Linking the nuclear and cytoplasmic compartments, the nuclear pore complex (NPC) is one of the cell's most essential and complex structures. Using an approach that integrates X-ray crystallography, small angle X-ray scattering (SAXS) and electron microscopy (EM) data, Almo, Rout, Sali and colleagues have produced atomic-level models for Saccharomyces cerevisiae (Sc) Nup133, a major component of the Nup84 complex in the NPC's outer ring. This work, from two PSI Centers (PSI NYSGRC and NPCXstals), aimed to solve the structure of this notoriously flexible protein and determine whether Nup133 contains a motif postulated to interact with the nuclear membrane.

Aided by the crystal structure of a related fungal VpNup13355–502 (PDB 4Q9T) and SAXS data, the authors built an initial model for full-length ScNup133. However, as the SAXS profile obtained for ScNup1332–1157 did not agree with that arising from the comparative model, the authors looked more carefully at the solution dynamics of ScNup1332–1157 and concluded that the data could only be explained by a multistate model. Comparison of the SAXS data and EM class averages resulted in a final model with four states, distinguished mainly by the relative positions of the N- and C-terminal domains; these states were confirmed by crosslinking/mass spectrometry and mutational analyses.

One feature noted in previous Nup133 structures was an unresolved loop in the seven-bladed β-propeller; it had been speculated to be an ArfGAP1 lipid packing sensor (ALPS) motif, which senses and stabilizes membrane curvature. Using a helical wheel representation, the ALPS motif was identified in ScNup133, as well as two copies in ScNup120, an ortholog that is also part of the Nup84 complex. The integrative approach outlined in this study permitted the authors to determine the structure of the major open state as well as three minor compact forms. In addition, the ability to isolate the ALPS motif in both Nup133 and Nup120 establishes how the Nup84 complex may be anchored within the nuclear envelope membrane, and rebuts the previous suggestion that only organisms with open mitosis may require such membrane contacts. These results also classify Nup133 and Nup120 as coat-like proteins, with the ALPS being an ancestral remnant of vesicle-coating complexes.

Angela K. Eggleston


  1. S.J. Kim et al. Integrative structure-function mapping of the nucleoporin Nup133 suggests a conserved mechanism for membrane anchoring of the nuclear pore complex.
    Mol Cell Proteomics 13, 2911-26 (2014). doi:10.1074/mcp.M114.040915

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health