6pmp

From Proteopedia

Crystal structure of a fragment of rat phospholipase Cepsilon EF3-RA1

Structural highlights

6pmp is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.73Å
Ligands:	CA
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PLCE1_RAT The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. In podocytes, is involved in the regulation of lamellipodia formation. Acts downtream of AVIL to allow ARP2/3 complex assembly (By similarity).[UniProtKB:Q9P212]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Phospholipase Cepsilon (PLCepsilon) generates lipid-derived second messengers at the plasma and perinuclear membranes in the cardiovascular system. It is activated in response to a wide variety of signals, such as those conveyed by Rap1A and Ras, through a mechanism that involves its C-terminal Ras association (RA) domains (RA1 and RA2). However, the complexity and size of PLCepsilon has hindered its structural and functional analysis. Herein, we report the 2.7 A crystal structure of the minimal fragment of PLCepsilon that retains basal activity. This structure includes the RA1 domain, which forms extensive interactions with other core domains. A conserved amphipathic helix in the autoregulatory X-Y linker of PLCepsilon is also revealed, which we show modulates activity in vitro and in cells. The studies provide the structural framework for the core of this critical cardiovascular enzyme that will allow for a better understanding of its regulation and roles in disease.

Structure of phospholipase Cepsilon reveals an integrated RA1 domain and previously unidentified regulatory elements.,Rugema NY, Garland-Kuntz EE, Sieng M, Muralidharan K, Van Camp MM, O'Neill H, Mbongo W, Selvia AF, Marti AT, Everly A, McKenzie E, Lyon AM Commun Biol. 2020 Aug 14;3(1):445. doi: 10.1038/s42003-020-01178-8. PMID:32796910^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations

reviews cite this structure

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References

↑ Czyzyk J, Brogdon JL, Badou A, Henegariu O, Preston Hurlburt P, Flavell R, Bottomly K. Activation of CD4 T cells by Raf-independent effectors of Ras. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6003-8. Epub 2003 Apr 29. PMID:12721365 doi:http://dx.doi.org/10.1073/pnas.1031494100
↑ Kelley GG, Kaproth-Joslin KA, Reks SE, Smrcka AV, Wojcikiewicz RJ. G-protein-coupled receptor agonists activate endogenous phospholipase Cepsilon and phospholipase Cbeta3 in a temporally distinct manner. J Biol Chem. 2006 Feb 3;281(5):2639-48. Epub 2005 Nov 28. PMID:16314422 doi:http://dx.doi.org/M507681200
↑ Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, Garg P, Verma R, Chaib H, Hoskins BE, Ashraf S, Becker C, Hennies HC, Goyal M, Wharram BL, Schachter AD, Mudumana S, Drummond I, Kerjaschki D, Waldherr R, Dietrich A, Ozaltin F, Bakkaloglu A, Cleper R, Basel-Vanagaite L, Pohl M, Griebel M, Tsygin AN, Soylu A, Muller D, Sorli CS, Bunney TD, Katan M, Liu J, Attanasio M, O'toole JF, Hasselbacher K, Mucha B, Otto EA, Airik R, Kispert A, Kelley GG, Smrcka AV, Gudermann T, Holzman LB, Nurnberg P, Hildebrandt F. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet. 2006 Dec;38(12):1397-405. Epub 2006 Nov 5. PMID:17086182 doi:http://dx.doi.org/ng1918
↑ Rugema NY, Garland-Kuntz EE, Sieng M, Muralidharan K, Van Camp MM, O'Neill H, Mbongo W, Selvia AF, Marti AT, Everly A, McKenzie E, Lyon AM. Structure of phospholipase Cepsilon reveals an integrated RA1 domain and previously unidentified regulatory elements. Commun Biol. 2020 Aug 14;3(1):445. doi: 10.1038/s42003-020-01178-8. PMID:32796910 doi:http://dx.doi.org/10.1038/s42003-020-01178-8