Hydrogen-bonding dynamics between adjacent blades in G-protein beta-subunit regulates GIRK channel activation.

ABSTRACT: Functionally critical domains in the betagamma-subunits of the G-protein (Gbetagamma) do not undergo large structural rearrangements upon binding to other proteins. Here we show that a region containing Ser(67) and Asp(323) of Gbetagamma is a critical determinant of G-protein-gated inwardly rectifying K(+) (GIRK) channel activation and undergoes only small structural changes upon mutation of these residues. Using an interactive experimental and computational approach, we show that mutants that form a hydrogen-bond between positions 67 and 323 do not activate a GIRK channel. We also show that in the absence of hydrogen-bonding between these positions, other factors, such as the displacement of the crucial Ggamma residues Pro(60) and Phe(61), can impair Gbetagamma-mediated GIRK channel activ

SUBMITTER: Mirshahi T 

PROVIDER: S-EPMC1414569 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature