Computationally designed GPCR quaternary structures bias signaling pathway activation.

ABSTRACT: Communication across membranes controls critical cellular processes and is achieved by receptors translating extracellular signals into selective cytoplasmic responses. While receptor tertiary structures can be readily characterized, receptor associations into quaternary structures are challenging to study and their implications in signal transduction remain poorly understood. Here, we report a computational approach for predicting receptor self-associations, and designing receptor oligomers with various quaternary structures and signaling properties. Using this approach, we designed chemokine receptor CXCR4 dimers with reprogrammed binding interactions, conformations, and abilities to activate distinct intracellular signaling proteins. In agreement with our predictions, the designed CXCR4

SUBMITTER: Paradis JS 

PROVIDER: S-EPMC9652377 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature