Rationally designed integrin beta3 mutants stabilized in the high affinity conformation.

ABSTRACT: Integrins are important cell surface receptors that transmit bidirectional signals across the membrane. It has been shown that a conformational change of the integrin beta-subunit headpiece (i.e. the beta I domain and the hybrid domain) plays a critical role in regulating integrin ligand binding affinity and function. Previous studies have used coarse methods (a glycan wedge, mutations in transmembrane contacts) to force the beta-subunit into either the open or closed conformation. Here, we demonstrate a detailed understanding of this conformational change by applying computational design techniques to select five amino acid side chains that play an important role in the energetic balance between the open and closed conformations of alphaIIbbeta3. Eight single-point mutants were designed a

SUBMITTER: Luo BH 

PROVIDER: S-EPMC2635054 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature