4QJ4

Structure of a fragment of human phospholipase C-beta3 delta472-569, bound to IP3 and in complex with Galphaq

Summary for 4QJ4

• Entry DOI: 10.2210/pdb4qj4/pdb
• Related: 4QJ3 4QJ5
• Descriptor: Guanine nucleotide-binding protein G(q) subunit alpha, 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3, GUANOSINE-5'-DIPHOSPHATE, ... (8 entities in total)
• Functional Keywords: gtp-binding protein alpha subunits, phospholipase c beta, ph domain, ef hand, c2 domain, tim barrel domain, gtp hydrolysis, g-protein signaling, lipase, calcium binding, gtp binding, phospholipids, membrane, signaling protein-hydrolase complex, signaling protein/hydrolase
• Biological source: Mus musculus (mouse); More
• Cellular location: Nucleus : P21279; Membrane; Peripheral membrane protein: Q01970
• Total number of polymer chains: 2
• Total formula weight: 136036.40

Authors

Lyon, A.M.,Tesmer, J.J.G. (deposition date: 2014-06-03, release date: 2014-10-22, Last modification date: 2023-09-20)

Primary citation

Lyon, A.M.,Begley, J.A.,Manett, T.D.,Tesmer, J.J.
Molecular mechanisms of phospholipase C beta 3 autoinhibition.
Structure, 22:1844-1854, 2014

PubMed Abstract: Phospholipase C β (PLCβ) enzymes are dramatically activated by heterotrimeric G proteins. Central to this response is the robust autoinhibition of PLCβ by the X-Y linker region within its catalytic core and by the Hα2' helix in the C-terminal extension of the enzyme. The molecular mechanism of each and their mutual dependence are poorly understood. Herein, it is shown that distinct regions within the X-Y linker have specific roles in regulating activity. Most important,an acidic stretch within the linker stabilizes a lid that occludes the active site, consistent with crystal structures of variants lacking this region. Inhibition by the Hα2' helix is independent of the X-Y linker and likely regulates activity by limiting membrane interaction of the catalytic core. Full activation of PLCβ thus requires multiple independent molecular events induced by membrane association of the catalytic core and by the binding of regulatory proteins.

PubMed: 25435326
DOI: 10.1016/j.str.2014.10.008

Experimental method

X-RAY DIFFRACTION (3.3 Å)