Catalysis by phospholipase C delta1 requires that Ca2+ bind to the catalytic domain, but not the C2 domain

Biochemistry
J A Grobler, J H Hurley

Abstract

The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide-specific phospholipase C (PLC) is absolutely dependent on Ca2+. The PH domain truncated catalytic core of rat phospholipase C delta1 (PLC-delta1) has Ca2+ binding sites in its catalytic and C2 domains, and potential Ca2+ binding sites in two EF-hands. A catalytically inactive PLC-delta1 catalytic core bound with low affinity to PIP2-containing vesicles in the presence of Ca2+. A mutant PLC-delta1 has been engineered which lacks the C2 domain Ca2+ binding site and the surrounding loops known as the jaws. Isothermal calorimetric titration showed four Ca2+ ions bind to the wild-type PLC-delta1 catalytic core in solution but only one binds to the C2 domain jaws deletion mutant. The activity and Ca2+ dependence of wild-type and mutant phospholipase Cs were determined using substrate incorporated in detergent micelles and in large unilamellar vesicles. The activities of wild-type and mutant were identical to each other in both assay systems. Wild-type and the C2 jaws deletion mutant of PLC have Hill coefficients of 1.12-1.16 with respect to [Ca2+]. We conclude that a single Ca2+ bound to the catalytic domain is entirely responsible for the Ca2+ depende...Continue Reading

References

Aug 11, 1995·The Journal of Biological Chemistry·G M CarmanE A Dennis
Aug 1, 1994·Quarterly Reviews of Biophysics·J J FalkeO B Peersen
Jan 1, 1993·Annual Review of Biophysics and Biomolecular Structure·A C Newton
Mar 8, 1996·The Journal of Biological Chemistry·E R ChapmanR Jahn
Jan 1, 1997·Annual Review of Biochemistry·W D SingerP C Sternweis
Apr 1, 1997·Molecular Membrane Biology·M Mosior, R M Epand

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Citations

Nov 26, 1999·Biochimica Et Biophysica Acta·R L Williams
Jul 20, 2005·Development, Growth & Differentiation·Andre KuliszSheldon S Shen
Nov 17, 2009·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Isao Matsuoka, Masaaki Ito
Jul 8, 1999·Proceedings of the National Academy of Sciences of the United States of America·T WangS Scarlata
Sep 14, 2013·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Hye Jin BakJoon Ki Chung
Nov 13, 2012·Annual Review of Physiology·Ganesh Kadamur, Elliott M Ross
Jun 20, 2012·Experimental Cell Research·Eric ChungMario Rebecchi
Jun 8, 2001·Annual Review of Biochemistry·S G Rhee
Jan 21, 2014·Biochimica Et Biophysica Acta·Senena Corbalan-Garcia, Juan C Gómez-Fernández
Jan 27, 1999·Biochimica Et Biophysica Acta·A K HinderliterC E Creutz
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·J H Hurley, S Misra
Nov 18, 2014·Frontiers in Cellular Neuroscience·Arthur P H de Jong, Diasynou Fioravante
Jul 31, 2013·Gene·Na Young KimJoon Ki Chung
Sep 25, 1999·The Journal of Biological Chemistry·M YamagaH Yagisawa
May 18, 2004·British Journal of Anaesthesia·M Zaugg, M C Schaub
Dec 22, 2017·The Journal of Biological Chemistry·Weigang HuangQisheng Zhang
Nov 14, 2001·The Journal of Biological Chemistry·Bharath AnanthanarayananWonhwa Cho
Oct 4, 2000·Physiological Reviews·M J Rebecchi, S N Pentyala
Sep 7, 2014·The Journal of Biological Chemistry·Thomas H CharpentierJohn Sondek
Aug 16, 2000·American Journal of Physiology. Cell Physiology·M C CilluffoN A Farahbakhsh
Jan 1, 2004·The Journal of Biological Chemistry·Zen KouchiShunichi Miyazaki

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