title: Full-length Gα(q)-phospholipase C-β3 structure reveals interfaces of the C-terminal coiled-coil domain.
abstract: Phospholipase C-β (PLCβ) is directly activated by Gαq, but the molecular basis for how its distal C-terminal domain (CTD) contributes to maximal activity is poorly understood. Herein we present both the crystal structure and cryo-EM three-dimensional reconstructions of human full-length PLCβ3 in complex with mouse Gαq. The distal CTD forms an extended monomeric helical bundle consisting of three antiparallel segments with structural similarity to membrane-binding bin-amphiphysin-Rvs (BAR) domains. Sequence conservation of the distal CTD suggests putative membrane and protein interaction sites, the latter of which bind the N-terminal helix of Gαq in both the crystal structure and cryo-EM reconstructions. Functional analysis suggests that the distal CTD has roles in membrane targeting and in optimizing the orientation of the catalytic core at the membrane for maximal rates of lipid hydrolysis.
authors: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors: Angeline M
authors: AM
authors: Lyon
authors: Somnath
authors: S
authors: Dutta
authors: Cassandra A
authors: CA
authors: Boguth
authors: Georgios
authors: G
authors: Skiniotis
authors: John J G
authors: JJ
authors: Tesmer
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D054799:Phospholipase C beta / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: C518039:PLCB3 protein, human; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
references: J Biol Chem. 2008 Dec 12;283(50):34923-34
references: 18936096
references: J Struct Biol. 1999 Dec 1;128(1):82-97
references: 10600563
references: Biochem J. 1997 Oct 15;327 ( Pt 2):431-7
references: 9359412
references: J Biol Chem. 1998 Jul 31;273(31):19772-7
references: 9677408
references: Mol Pharmacol. 2011 Sep;80(3):434-45
references: 21693623
references: Nat Struct Biol. 2002 Jan;9(1):32-6
references: 11753430
references: Nature. 1997 Sep 18;389(6648):290-3
references: 9305844
references: Curr Biol. 2010 Aug 10;20(15):1327-35
references: 20579885
references: Annu Rev Biochem. 2011;80:101-23
references: 21438688
references: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7971-5
references: 9223297
references: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9
references: 20457744
references: Eur J Biochem. 1993 Nov 1;217(3):1109-15
references: 8223634
references: J Comput Chem. 2004 Oct;25(13):1605-12
references: 15264254
references: J Mol Cell Cardiol. 2010 Aug;49(2):221-33
references: 20036247
references: Science. 2010 Nov 12;330(6006):974-80
references: 20966218
references: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83
references: 17452350
references: J Biol Chem. 2002 Feb 8;277(6):4294-300
references: 11729196
references: J Biol Chem. 1996 Jan 5;271(1):496-504
references: 8550609
references: Cell Signal. 2013 Jan;25(1):255-63
references: 23006664
references: Methods Enzymol. 1997;276:307-26
references: 27754618
references: Methods Mol Biol. 2004;237:67-75
references: 14501039
references: J Biol Chem. 1993 May 5;268(13):9667-74
references: 8387502
references: J Biol Chem. 1993 Feb 15;268(5):3704-9
references: 8381437
references: Nature. 2009 Jan 29;457(7229):599-602
references: 19078957
references: Eur J Neurosci. 2007 Feb;25(3):659-72
references: 17298601
references: Nat Rev Mol Cell Biol. 2007 Jan;8(1):74-84
references: 17183362
references: Curr Drug Targets. 2010 Aug;11(8):1032-40
references: 20426766
references: J Biol Chem. 1996 Aug 30;271(35):21187-92
references: 8702889
references: EMBO J. 1986 Apr;5(4):823-6
references: 3709526
references: Subcell Biochem. 2012;58:61-94
references: 22403074
references: Science. 2004 Jan 23;303(5657):495-9
references: 14645856
references: FASEB J. 2009 Oct;23(10):3564-70
references: 19564249
references: J Biol Chem. 2011 Jan 14;286(2):942-51
references: 21036901
references: Biotechniques. 2004 Feb;36(2):276-85
references: 14989092
references: Annu Rev Physiol. 2013;75:127-54
references: 23140367
references: Nat Struct Mol Biol. 2011 Aug 07;18(9):999-1005
references: 21822282
references: Cardiovasc Res. 2009 May 1;82(2):286-95
references: 18940816
references: Science. 1991 Feb 15;251(4995):804-7
references: 1846707
references: J Biol Chem. 1992 Dec 15;267(35):25451-6
references: 1460039
references: Nature. 1991 Apr 11;350(6318):516-8
references: 1707501
references: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
references: 11517324
references: J Cell Sci. 2008 Nov 15;121(Pt 22):3770-7
references: 18957514
references: J Biol Chem. 1996 Oct 11;271(41):25071-8
references: 8810260
references: Methods Enzymol. 2003;374:300-21
references: 14696379
references: Am J Physiol Heart Circ Physiol. 2008 Nov;295(5):H2135-42
references: 18820027
references: Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H719-27
references: 15072958
references: J Biol Chem. 1998 May 8;273(19):11650-9
references: 9565585
references: Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10385-90
references: 10468617
references: EMBO J. 1998 Nov 2;17(21):6241-9
references: 9799233
references: Nature. 1996 Apr 18;380(6575):595-602
references: 8602259
references: Nat Struct Mol Biol. 2006 Dec;13(12):1135-40
references: 17115053
references: Mol Cell. 2008 Aug 8;31(3):383-94
references: 18691970
references: EMBO J. 2011 Aug 31;30(17):3501-15
references: 21878992
references: J Biol Chem. 1993 Feb 15;268(5):3710-4
references: 8429045
references: J Biol Chem. 1993 Dec 5;268(34):25952-7
references: 8245028
references: FASEB J. 2008 Aug;22(8):2768-74
references: 18390926
references: Biochemistry. 1999 Feb 2;38(5):1517-24
references: 9931017