An autoinhibitory helix in the C-terminal region of phospholipase C-β mediates Gαq activation

被引：60

作者：

Lyon, Angeline M. ^{[1
]}

Tesmer, Valerie M. ^{[1
]}

Dhamsania, Vishan D. ^{[1
]}

Thal, David M. ^{[1
]}

Gutierrez, Joanne ^{[2
]}

Chowdhury, Shoaib ^{[2
]}

Suddala, Krishna C. ^{[3
]}

Northup, John K. ^{[2
]}

Tesmer, John J. G. ^{[1
,4
]}

机构：

[1] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA

[2] Natl Inst Deafness & Other Commun Disorders, Cell Biol Lab, US Natl Inst Hlth, Rockville, MD USA

[3] Univ Michigan, Dept Biophys, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2011年 / 18卷 / 09期

基金：

美国国家卫生研究院;

关键词：

G-PROTEIN; MEMBRANE-BINDING; ALPHA-SUBUNIT; GAMMA-SUBUNIT; PURIFICATION; C-BETA-1; DOMAIN; G(Q); PLC; ISOZYMES;

D O I：

10.1038/nsmb.2095

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The enzyme phospholipase C-beta (PLC beta) is a crucial regulator of intracellular calcium levels whose activity is controlled by heptahelical receptors that couple to members of the G(q) family of heterotrimeric G proteins. We have determined atomic structures of two invertebrate homologs of PLC beta (PLC21) from cephalopod retina and identified a helix from the C-terminal regulatory region that interacts with a conserved surface of the catalytic core of the enzyme. Mutations designed to disrupt the analogous interaction in human PLC beta 3 considerably increase basal activity and diminish stimulation by G alpha(q). G alpha(q) binding requires displacement of the autoinhibitory helix from the catalytic core, thus providing an allosteric mechanism for activation of PLC beta.

引用

页码：999 / U54

页数：8

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