GxxxG motifs, phenylalanine, and cholesterol guide the self-association of transmembrane domains of ErbB2 receptors.

ABSTRACT: GxxxG motifs are common in transmembrane domains of membrane proteins and are often introduced to artificial peptides to inhibit or promote association to stable structures. The transmembrane domain of ErbB2 presents two separate such motifs that are proposed to be connected to stability and activity of the dimer. Using molecular simulations, we show that these sequences play a critical role during the recognition stage, forming transient complexes that lead to stable dimers. In pure phospholipid bilayers association occurs by contacts formed at the C-terminus promoted by the presence of phenylalanine residues. Helices subsequently rotate to eventually pack at short separations favored by lipid entropic contributions. In contrast, at intermediate cholesterol concentrations, a different pat

SUBMITTER: Prakash A 

PROVIDER: S-EPMC3192960 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature