Send to

Choose Destination
See comment in PubMed Commons below
Protein Sci. 2013 Jun;22(6):745-54. doi: 10.1002/pro.2258. Epub 2013 May 8.

Structure-based network analysis of an evolved G protein-coupled receptor homodimer interface.

Author information

Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093-0365, USA.


Crystallographic structures and experimental assays of human CXC chemokine receptor type 4 (CXCR4) provide strong evidence for the capacity to homodimerize, potentially as a means of allosteric regulation. Even so, how this homodimer forms and its biological significance has yet to be fully characterized. By applying principles from network analysis, sequence-based approaches such as statistical coupling analysis to determine coevolutionary residues, can be used in conjunction with molecular dynamics simulations to identify residues relevant to dimerization. Here, the predominant coevolution sector lies along the observed dimer interface, suggesting functional relevance. Furthermore, coevolution scoring provides a basis for determining significant nodes, termed hubs, in the network formed by residues found along the interface of the homodimer. These node residues coincide with hotspots indicating potential druggability. Drug design efforts targeting such key residues could potentially result in modulation of binding and therapeutic benefits for disease states, such as lung cancers, lymphomas and latent HIV-1 infection. Furthermore, this method may be applied to any protein-protein interaction.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center