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

Journal Article · Thu Aug 21 00:00:00 EDT 2014 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/nsmb.2497· OSTI ID:1069135

Lyon, Angeline M.; Dutta, Somnath; Boguth, Cassandra A.; Skiniotis, Georgios; Tesmer, John J.G. ^[1]

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1. Michigan

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

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: AHAOTHERUNIVERSITYNIH
• OSTI ID: 1069135
• Journal Information: Nature Structural & Molecular Biology, Vol. 20, Issue (3) ; 03, 2013; ISSN 1545-9993
• Publisher: Nature Publishing Group
• Country of Publication: United States
• Language: ENGLISH