Full-length G?(q)-phospholipase C-?3 structure reveals interfaces of the C-terminal coiled-coil domain.

ABSTRACT: Phospholipase C-? (PLC?) is directly activated by G?q, but the molecular basis for how its distal C-terminal domain (CTD) contributes to maximal activity is poorly understood. Herein we present both the crystal structure and cryo-EM three-dimensional reconstructions of human full-length PLC?3 in complex with mouse G?q. The distal CTD forms an extended monomeric helical bundle consisting of three antiparallel segments with structural similarity to membrane-binding bin-amphiphysin-Rvs (BAR) domains. Sequence conservation of the distal CTD suggests putative membrane and protein interaction sites, the latter of which bind the N-terminal helix of G?q in both the crystal structure and cryo-EM reconstructions. Functional analysis suggests that the distal CTD has roles in membrane targeting and in optimizing the orientation of the catalytic core at the membrane for maximal rates of lipid hydrolysis.

SUBMITTER: Lyon AM 

PROVIDER: S-EPMC3594540 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature