Mutations affecting the oligomerization interface of G-protein-coupled receptors revealed by a novel de novo protein design framework.

ABSTRACT: Specific functional and pharmacological properties have recently been ascribed to G-protein-coupled receptor (GPCR) dimers/oligomers. Because the association of two identical or two distinct GPCR monomers seems to be required to elicit receptor function, it is necessary to understand the exact nature of this interaction. We present here a novel method for de novo protein design and its application to the prediction of mutations that can stabilize or destabilize a GPCR dimer while maintaining the monomer's native fold. To test the efficacy of this new method, the dimer of the single-spanned transmembrane domain of glycophorin A was used as a model system. Experimental data from mutagenesis of the helix-helix interface are compared with computational predictions at that interface, and the mo

SUBMITTER: Taylor MS 

PROVIDER: S-EPMC2267121 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature