Structure of the XXXX ( @entity72791 )-Gaq Complex: Molecular Basis for Ga Selectivity.

@entity3007 @entity18232 @entity72792 @entity18151 @entity72791
UNASSIGNED: @entity18151 ( @entity18151 ) proteins interact with activated Ga subunits via their @entity18151 domains and accelerate the hydrolysis of @entity3007 . Whereas the R4 subfamily of @entity18151 proteins generally accepts both Gai/o and Gaq/11 subunits as substrates, the R7 and R12 subfamilies select against Gaq/11. In contrast, only one @entity18151 protein, @entity18232 , is known to be selective for Gaq/11. The molecular basis for this selectivity is not clear. Previously, the crystal structure of @entity18232 in complex with Gaq revealed a non-canonical interaction that could be due to interfacial differences imposed by @entity18232 , the Ga subunit, or both. To resolve this ambiguity, the 2.6    crystal structure of @entity72791 , an R4 subfamily member, was determined in complex with Gaq. @entity72791 adopts the same pose on Gaq as it does when bound to Gai3, indicating that the non-canonical interaction of @entity18232 with Gaq is due to unique features of @entity18232 . Based on the @entity72791 structure, residues in @entity72791 that contact a unique a-helical domain loop of Gaq were converted to those typically found in R12 subfamily members, and the reverse substitutions were introduced into @entity72792 , an R12 subfamily member. Although these substitutions perturbed their ability to stimulate GTP hydrolysis, they did not reverse selectivity. Instead, selectivity for Gaq seems more likely determined by whether strong contacts can be maintained between a of the @entity18151 domain and Switch III of Gaq, regions of high sequence and conformational diversity in both protein families.
