PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Signaling: A Platform for Opposing Functions
May 2015
Protein Folding and Misfolding: It's the Journey, Not the Destination
March 2015
Molecular Portraits of the Cell
February 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
Updating ModBase
January 2015
Transmembrane Spans
December 2014
Mining Protein Dynamics
May 2014
Novel Proteins and Networks: Assigning Function
May 2014
Cancer Networks: Predicting Catalytic Residues from 3D Protein Structures
November 2013
The Immune System: A Brotherhood of Immunoglobulins
June 2013
The Immune System: Super Cytokines
June 2013
Infectious Diseases: Targeting Meningitis
May 2013
PDZ Domains
April 2013
Protein Interaction Networks: Adding Structure to Protein Networks
April 2013
Design and Discovery: Flexible Backbone Protein Redesign
February 2013
Pocket changes
July 2012
Predictive protein origami
July 2012
Refining protein structure prediction
March 2012
Metal mates
February 2012
Devil is in the details
January 2012
Playing while you work
November 2011
Docking and rolling
October 2011
Fit to serve
October 2011
Rosetta hone
July 2011
Structure from sequence
July 2011
An easier solution for symmetry
June 2011
Solutions in the solution
June 2011
Regulating nitrogen assimilation
January 2011
Guard cells pick up the SLAC
December 2010
Alpha/Beta Barrels
October 2010
Modeling RNA structures
May 2010
Deducing function from small structural clues
February 2010
Spot the pore
January 2010
Network coverage
November 2009
GPCR modeling: any good?
August 2009
Protein modeling made easy
July 2009
Model proteins in your lunch break
April 2009
Click for cancer-protein interactions
December 2008
Modeling with SAXS
October 2008
Designing activity
September 2008

Technology Topics Modeling

Piecing Together the Nuclear Pore Complex

SBKB [doi:10.3942/psi_sgkb/fm_2015_2]
Featured System - February 2015
Short description: PSI researchers have solved another piece in the puzzle for revealing an atomic-level model of the nuclear pore complex.

Scientists are exploring larger and larger molecular machines by combining the many tools of integrative structural biology. The nuclear pore complex has been a subject of this study for many years, revealing an increasingly detailed view. It is a challenging subject for many reasons: it is highly dynamic as it performs its duty of transporting molecules in and out of the nucleus, and by molecular standards, it is huge, comprised of over 450 protein subunits. The complex has been studied extensively by electron microscopy, revealing a characteristic eight-fold symmetric ring crossing the nuclear membrane (shown here from entry EMD2444 at the EMDataBank). More recently, researchers are determining the atomic structures of the individual components, and using them to reconstruct the whole complex.

Flexible Nucleoporins

PSI researchers at NYSGRC have recently determined the structure of Nup192, a nucleoporin protein that forms part of the inner ring of the nuclear pore complex. The structure reveals a protein that folds into three domains, each composed of a collection of alpha helices, shown here from PDB entry 4ifq. Several lines of evidence reveal that the protein is quite flexible, including SAXS and EM studies of the isolated protein and molecular dynamics computations on the structure. This motion may help the nuclear pore complex flex to accommodate cargo of different sizes as they pass through the pore.

Nup192 Reconstruction

As is often the case with flexible proteins, PSI researchers needed to use a divide-and-conquer approach with this nucleoporin. They determined the atomic structure of half of the protein, and combined this with electron microscopy to reconstruct a model for the entire protein. A 3D tomographic reconstruction of the protein, shown here from entry EMD5556 at the EMDataBank, reveals a long structure shaped like a question mark. The atomic structure fits nicely into the hook-shaped end of the reconstruction.

Distant Cousins

Comparison of the Nup192 structure revealed a possible evolutionary relationship to other proteins involved in cellular trafficking. As we might expect, the yeast Nup192 structure solved by PSI researchers is quite similar to a recent structure of fungal Nup192, PDB entry 4knh. More distant relatives, which all show a similar pattern of alpha-helical domains, include karyopherins such as Kap-alpha shown here (PDB entry 1ee4), as well as beta-catenin and adaptor protein 1. To explore these structures in more detail, the JSmol tab below displays an interactive JSmol.

Nup192 and Relatives (PDB entries 4ifq, 4knh, 1ee4, 1ibr, 1qz7 & 1w63)

Two structures of Nup192 and several structurally related proteins are overlapped here. Notice the similar folding pattern comprised of alpha-helical domains. Use the buttons to switch between the proteins and change the representation.


  1. 4knh: Stuwe, T., Lin, D. H., Collins, L. N., Hurt, E. & Hoelz, A. Evidence for an evolutionary relationship between the large adaptor protein Nup192 and karyopherins. Proc. Natl. Acad. Sci. USA 111, 2530-2535 (2014).

  2. 4ifq: Sampathkumar, P., et al. Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex. Structure 21, 560-571 (2013).

  3. Bui, K. H., et al. Integrated structural analysis of the human nuclear pore complex scaffold. Cell 155, 1233-1243 (2013).

  4. Heldwein, E. et al. Crystal structure of the clathrin adaptor protein 1 core. Proc. Natl. Acad. Sci. USA 101, 14108-14113 (2004).

  5. 1qz7: Xing, Y, Clements, W. K., Kimelman, D. & Xu, W. Crystal structure of a beta- catenin/axin complex suggests a mechanism for the beta-catenin destruction complex. Genes Dev. 17, 2753-2764 (2003).

  6. 1ee4: Conti, E. & Kuriyan, J. Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. Structure Fold. Des. 8, 329-338 (2000).

  7. Vetter, I. R., Arndt, A., Kutay, U., Gorlich, D. & Wittinghofer, A. Structural view of the Ran-importin beta interaction at 2.3 A resolution. Cell 97, 635-646 (1999).

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