Full-length Gαq–phospholipase C-β3 structure reveals interfaces of the C-terminal coiled-coil domain

• DOI: 10.1038/nsmb.2497
• Publication Date: 2013-02-03T19:21:36Z
• Authors: Angeline M Lyon; Somnath Dutta; Cassandra A Boguth; Georgios Skiniotis; John J G Tesmer
• Keywords: Models, Molecular; 0303 health sciences; Protein Conformation; Cryoelectron Microscopy; Phospholipase C beta; Crystallography, X-Ray; Article; Protein Structure, Tertiary; Mice; 03 medical and health sciences; Catalytic Domain; Animals; GTP-Binding Protein alpha Subunits, Gq-G11; Humans

Phospholipase C-β (PLCβ) is directly activated by Gαq, 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 PLCβ3 in complex with mouse Gαq. 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 Gαq 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.