Phospholipase C

From Proteopedia

Function Phospholipase C (PLC) cleaves phospholipids before the phosphate group. PLCs catalyze the conversion of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol.[1] Phospholipase C β is a key enzyme in mammalian taste signal transduction[2]. For more details on phospholipase C β see PLC beta 3 Gq. Phospholipase C γ is a physiological guanine nucleotide exchange factor for the nuclear GTPase[3]. Phospholipase C δ is critical for Ca+2 homeostasis. Phospholipase C ε is an effector for Ras. Phosphatidylinositol-specific phospholipase C (PIPLC) catalyzes the hydrolysis of phosphatidylinositol into inositol triphosphate and deacylglycerol. PIPLC functions at the plasma membrane. PIPLC can release phosphatidylinositol-linked proteins (i.e., acetylcholinesterase) from the membrane by enzymatically cleaving their GPI anchor. [4]. See also IP3 is second messenger. Disease Phospholipase C γ gene blocking can stop breast cancer.[5] Phospholipase C δ has important suppressive role in the development and progression of esophageal carcinoma. Mutations in phospholipase C δ1 cause hereditary leukonychia[6]. Mutations in phospholipase C ε1 are associated with stomach cancer risk and nephrotic syndromes[7]. Structural highlights The active site of PIPLC is located at a solvent-accessible cleft at the C-terminal.[8] Solvent-accessible cleft.

spinqualitylabelsall models Structure of phosphatidylinositol-specific phospholipase C complex with myo-inositol (PDB code 1ptg). Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D structures of phospholipase C

Updated on 28-August-2023

PIPLC

1ptd – BcPIPLC – Bacillus cereus

2ptd, 3ptd, 4ptd, 5ptd, 6ptd, 7ptd – BcPIPLC (mutant)

2plc – LmPIPLC – Listeria monocytogenes

3ea1 – BtPIPLC – Bacillus thuringiensis

1t6m, 2or2, 3ea3 – BtPIPLC (mutant)

3v18 – SaPIPLC – Staphylococcus aureus

4f2t, 4f2u, 4i8y, 4i9m – SaPIPLC (mutant)

5fyo, 5fyp – PsPIPLC – Pseudomonas

PIPLC complex

1ptg – BcPIPLC + myo-inositol

1gym – BcPIPLC + glucosamine-myo-inositol

1aod – LmPIPLC + myo-inositol

3ea2 – BtPIPLC + myo-inositol

5fyr – PsPIPLC + myo-inositol

3v16, 4f2b, 4rv3 – SaPIPLC + myo-inositol

3v1h, 4i9t, 4s3g – SaPIPLC (mutant) + myo-inositol

4i90 – SaPIPLC (mutant) + choline

4i9j – SaPIPLC (mutant) + diC4PC

Phospholipase C β

2zkm – hPLCB-2 - human

2fju – hPLCB-2 + RAC1

8emv – hPLCB-3 – Cryo EM

7sq2, 4gnk, 4qj3 – hPLCB-3 + guanine nucleotide-binding protein G subunit alpha

4qj4, 4qj5 – hPLCB-3 + guanine nucleotide-binding protein G subunit alpha + inositol phosphate derivative

7sq2 – hPLCB-3 + guanine nucleotide-binding protein G subunit alpha + GDP

8emw, 8emx – hPLCB-3 + guanine nucleotide-binding protein G subunits beta+gamma – Cryo EM

1jad – PLCB - turkey

3qr0 – PLCB - cuttlefish

3qr1 – PLCB - squid

Phospholipase C γ

1hsq, 2hsp – hPLCG SH3 domain - NMR

4fbn – hPLCG-1

2k2j – hPLCG-2 split PH2 domain - NMR

2w2w – hPLCG-2 split PH2 domain (mutant)

2w2x – hPLCG-2 split PH2 domain + RAC2 br />

4ey0 – hPLCG-1 SH2 domain (mutant)

7nxe – hPLCG-1 SH2 domain + peptide

2pld, 2ple – PLCG C terminal SH2 domain + PDGF peptide – bovine - NMR

6pbc – rPLCG-1 – rat

1ywp – rPLCG-1 SH3 domain 790-851

1y0m – rPLCG-1 SH3 domain (mutant)

2fjl – rPLCG-1 split PH2 domain - NMR

2eob – rPLCG-2 SH2 domain 633-743 - NMR

1ywo – rPLCG-1 SH3 domain + lymphocyte cytosolic protein peptide

7z3j – rPLCG-1 + inositol-3P

4k44, 4k45 – rPLCG C terminal SH2 domain

2dx0 – mPLCG-2 N terminal SH2 domain – mouse

2eqi – mPLCG-2 SH3 domain - NMR

Phospholipase C δ

1mai – rPLCD-1 PH domain + inositol triphosphate

1qas, 1qat, 1djg, 1djh, 1dji, 2isd – rPLCD-1

1djx, 1djy – rPLCD-1 + inositol triphosphate

1djz, 1djw – rPLCD-1 + inositol phosphate derivative

Phospholipase C ε

2bye – hPLCE-1 RA1 domain - NMR

2byf – hPLCE-1 RA2 domain - NMR

6pmp – rPLCE-1 RA1 domain

Phospholipase C

8hav, 8haw – BcPLC4 (mutant) – Arabidopsis thaliana

1ah7 – BcPLC

1p5x, 2ffz, 2fgn, 2huc – BcPLC (mutant)

1p6d, 1p6e – BcPLC (mutant) + phosphocholine derivative

1ca1, 1qm6, 1qmd, 1gyg, 1kho, 2wxt – CpPLC – Clostridium perfringensbr />

2wxu, 2wy6 – CpPLC (mutant)

References

1. ↑ Barr AJ, Marjoram R, Xu J, Snyderman R. Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3. Biochem Biophys Res Commun. 2002 Apr 26;293(1):647-52. PMID:12054652 doi:http://dx.doi.org/10.1016/S0006-291X(02)00259-0
2. ↑ Yasuoka A, Aihara Y, Matsumoto I, Abe K. Phospholipase C-beta 2 as a mammalian taste signaling marker is expressed in the multiple gustatory tissues of medaka fish, Oryzias latipes. Mech Dev. 2004 Jul;121(7-8):985-9. PMID:15210203 doi:http://dx.doi.org/10.1016/j.mod.2004.03.009
3. ↑ Ye K, Aghdasi B, Luo HR, Moriarity JL, Wu FY, Hong JJ, Hurt KJ, Bae SS, Suh PG, Snyder SH. Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE. Nature. 2002 Jan 31;415(6871):541-4. PMID:11823862 doi:http://dx.doi.org/10.1038/415541a
4. ↑ Mortara RA, Minelli LM, Vandekerckhove F, Nussenzweig V, Ramalho-Pinto FJ. Phosphatidylinositol-specific phospholipase C (PI-PLC) cleavage of GPI-anchored surface molecules of Trypanosoma cruzi triggers in vitro morphological reorganization of trypomastigotes. J Eukaryot Microbiol. 2001 Jan-Feb;48(1):27-37. PMID:11249190
5. ↑ Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, Rossi C, Iezzi M, Lattanzio R, Piantelli M, Iacobelli S, Broggini M, Falasca M. Phospholipase Cgamma1 is required for metastasis development and progression. Cancer Res. 2008 Dec 15;68(24):10187-96. doi: 10.1158/0008-5472.CAN-08-1181. PMID:19074886 doi:http://dx.doi.org/10.1158/0008-5472.CAN-08-1181
6. ↑ Mir H, Khan S, Arif MS, Ali G, Wali A, Ansar M, Ahmad W. Mutations in the gene phospholipase C, delta-1 (PLCD1) underlying hereditary leukonychia. Eur J Dermatol. 2012 Nov-Dec;22(6):736-9. doi: 10.1684/ejd.2012.1852. PMID:23149345 doi:http://dx.doi.org/10.1684/ejd.2012.1852
7. ↑ . Editorial: The glue-ear syndrome. Lancet. 1975 Aug 30;2(7931):397-8. PMID:51196
8. ↑ Heinz DW, Ryan M, Bullock TL, Griffith OH. Crystal structure of the phosphatidylinositol-specific phospholipase C from Bacillus cereus in complex with myo-inositol. EMBO J. 1995 Aug 15;14(16):3855-63. PMID:7664726