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

An effective and cooperative dimer

SBKB [doi:10.1038/sbkb.2011.46]
Featured Article - November 2011
Short description: NMR studies reveal the dimer interface of the effector domain (ED) of NS1A from influenza A virus and provide insight into how dimerization of the ED provides cooperative dsRNA binding and other functions of NS1A.

Working model useful in guiding studies of the cooperative binding of NS1A to dsRNA. View into the dsRNA helical axis of a model of the complex between full-length NS1A and dsRNA (black). The RBD and ED domains are rendered as cylinders and surfaces, respectively. Image courtesy of James Aramini and Guy Montelione.

With the rise of new strains of influenza virus and the emergence of antiviral-resistant strains, identifying new targets for antiviral therapeutics is becoming increasingly important. One such target is the nonstructural protein 1 of influenza A (NS1A). NS1A binds nonspecifically to double-stranded RNA (dsRNA) through its N-terminal RNA-binding domain (RBD) and to a host of cellular proteins through its C-terminal effector domain (ED). These interactions allow the virus to evade the host antiviral system by affecting interferon-induced and other innate immune response pathways.

NS1A has been the focus of several recent structural studies. The ED has been shown to adopt a novel α-helix β-crescent fold that forms a homodimer. However, the biological dimer interface has remained controversial, as structures of the ED of NS1A from different influenza strains have revealed three different dimer interfaces.

Aramini, Ma, Montelione and colleagues (PSI NESG), in a PSI Community Outreach project with R. Krug at the University of Texas, Austin, have recently revealed the biologically relevant dimer of the ED from NS1A of H3N2 influenza A/Udorn/307/1972 (Ud) virus. They determined that the affinity for dimerization is relatively weak (micromolar range) and proceeded to map the dimer interface by NMR. Rotational correlation measurements, chemical shift mapping and NOE analysis all confirm a helix-helix dimer interface. These data are consistent with some, but not all, of the available crystal structures of the NS1A ED, resolving a controversy in the literature in which several alternative dimer interfaces have been observed in various crystal forms.

The authors went on to confirm the importance of a particular residue, Trp187, for dimerization. Mutation of Trp187 in the context of full-length Ud NS1A disrupts higher-order oligomerization and impairs its ability to bind to dsRNA. The mutant NS1A protein also shows reduced cooperativity in its binding of long stretches of dsRNA. On the basis of these results, Aramini and colleagues propose a model by which Ud NS1A forms a tube around the dsRNA, and the ED is involved in either cooperative interactions between NS1A dimers along the dsRNA, or in binding to other proteins, depending on the local NS1A, dsRNA and binding-partner concentrations.

This study highlights the ability of NMR to characterize weak dimers in solution, which are sometimes incorrectly characterized by crystallography as a result of lattice-packing effects. Furthermore, knowing the affinity for dimerization of the ED of Ud NS1A will be important for drug screening, as such experiments can be done under conditions at which the ED of Ud NS1A is monomeric.

Jennifer Cable


  1. J. M. Aramini, L.-C. Ma et al. The dimer interface of the effector domain of non-structural protein 1 from influenza A virus: an interface with multiple functions.
    J. Biol. Chem. 286, 26050-26060 (2011). doi:10.1074/jbc.M111.248765

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