title: X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil.
abstract: Transient receptor potential (TRP) channels comprise a large family of tetrameric cation-selective ion channels that respond to diverse forms of sensory input. Earlier studies showed that members of the TRPM subclass possess a self-assembling tetrameric C-terminal cytoplasmic coiled-coil domain that underlies channel assembly and trafficking. Here, we present the high-resolution crystal structure of the coiled-coil domain of the channel enzyme TRPM7. The crystal structure, together with biochemical experiments, reveals an unexpected four-stranded antiparallel coiled-coil architecture that bears unique features relative to other antiparallel coiled-coils. Structural analysis indicates that a limited set of interactions encode assembly specificity determinants and uncovers a previously unnoticed segregation of TRPM assembly domains into two families that correspond with the phylogenetic divisions seen for the complete subunits. Together, the data provide a framework for understanding the mechanism of TRPM channel assembly and highlight the diversity of forms found in the coiled-coil fold.
authors.affiliation: Cardiovascular Research Institute, Departments of Biochemistry and Biophysics and Cellular and Molecular Pharmacology, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, CA 94158-2330, USA.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Minor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D012996:Solutions / Q000737:chemistry; D055672:Static Electricity; D050053:TRPM Cation Channels / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D012996:Solutions; D050053:TRPM Cation Channels; C486584:Trpm7 protein, rat
references.citation: J Biol Chem. 1993 Sep 15;268(26):19218-27
references.pmid: 8366074
references.citation: Protein Eng. 2001 Dec;14(12):993-1000
references.pmid: 11809930
references.citation: J Biol Chem. 2005 Feb 18;280(7):6138-48
references.pmid: 15561722
references.citation: Mol Cell. 2001 May;7(5):1047-57
references.pmid: 11389851
references.citation: Nat Genet. 1997 Jun;16(2):179-83
references.pmid: 9171830
references.citation: Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
references.pmid: 15299374
references.citation: Structure. 2006 Feb;14(2):247-55
references.pmid: 16472744
references.citation: Science. 1992 Aug 28;257(5074):1225-30
references.pmid: 1519059
references.citation: Circ Res. 2005 Feb 4;96(2):207-15
references.pmid: 15591230
references.citation: Biochemistry. 2006 Apr 11;45(14):4463-73
references.pmid: 16584182
references.citation: Cell. 2000 Sep 1;102(5):657-70
references.pmid: 11007484
references.citation: Nat Struct Biol. 2000 May;7(5):403-7
references.pmid: 10802739
references.citation: Curr Biol. 2005 Apr 12;15(7):667-71
references.pmid: 15823540
references.citation: Science. 1993 Nov 26;262(5138):1401-7
references.pmid: 8248779
references.citation: Neuron. 2006 Nov 9;52(3):485-96
references.pmid: 17088214
references.citation: Science. 2005 Aug 5;309(5736):897-903
references.pmid: 16002581
references.citation: Nature. 2002 Nov 14;420(6912):193-8
references.pmid: 12432397
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6965-70
references.pmid: 9192675
references.citation: Handb Exp Pharmacol. 2007;(179):313-28
references.pmid: 17217066
references.citation: EMBO J. 1997 Nov 3;16(21):6337-45
references.pmid: 9400421
references.citation: Nat Genet. 2002 Jun;31(2):171-4
references.pmid: 12032570
references.citation: Neuron. 2007 Mar 1;53(5):663-75
references.pmid: 17329207
references.citation: Nat Neurosci. 2002 Nov;5(11):1169-76
references.pmid: 12368808
references.citation: J Biol Chem. 2001 Jul 27;276(30):28613-9
references.pmid: 11358970
references.citation: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7451-5
references.pmid: 18490661
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19524-9
references.pmid: 17158800
references.citation: J Mol Biol. 2005 May 6;348(3):777-87
references.pmid: 15826670
references.citation: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references.pmid: 15299926
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7692-5
references.pmid: 18509058
references.citation: EMBO J. 2003 Feb 3;22(3):395-403
references.pmid: 12554641
references.citation: Nat Genet. 2002 Jun;31(2):166-70
references.pmid: 12032568
references.citation: Nature. 2001 May 31;411(6837):595-9
references.pmid: 11385575
references.citation: Structure. 2005 May;13(5):703-12
references.pmid: 15893661
references.citation: Neuron. 1999 May;23(1):7-10
references.pmid: 10402187
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5509-13
references.pmid: 12700356
references.citation: Nat Struct Biol. 1999 Jan;6(1):38-43
references.pmid: 9886290
references.citation: Nature. 2001 May 31;411(6837):590-5
references.pmid: 11385574
references.citation: Org Lett. 2005 Feb 3;7(3):395-8
references.pmid: 15673248
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: J Biol Chem. 2005 Nov 11;280(45):37763-71
references.pmid: 16150690
references.citation: EMBO J. 2003 Feb 17;22(4):776-85
references.pmid: 12574114
references.citation: Am J Physiol Heart Circ Physiol. 2008 Mar;294(3):H1103-18
references.pmid: 18192217
references.citation: Pflugers Arch. 2005 Oct;451(1):235-42
references.pmid: 16025303
references.citation: Bioinformatics. 2006 Feb 1;22(3):356-8
references.pmid: 16317077
references.citation: Curr Opin Struct Biol. 2001 Aug;11(4):450-7
references.pmid: 11495738
references.citation: Biochemistry. 1974 Jul 30;13(16):3350-9
references.pmid: 4366945
references.citation: J Biol Chem. 2008 Feb 29;283(9):5815-30
references.pmid: 18165683
references.citation: Science. 1996 Mar 1;271(5253):1247-54
references.pmid: 8638105
references.citation: Nature. 1998 Apr 30;392(6679):945-8
references.pmid: 9582078
references.citation: J Physiol. 2008 Apr 1;586(7):1803-10
references.pmid: 18218681
references.citation: J Gen Physiol. 2006 May;127(5):525-37
references.pmid: 16636202
references.citation: Neuron. 2006 Jul 20;51(2):201-12
references.pmid: 16846855
references.citation: Adv Protein Chem. 2005;70:79-112
references.pmid: 15837514
references.citation: J Biol Chem. 2006 Dec 15;281(50):38396-404
references.pmid: 17065148
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2005 Apr;371(4):307-14
references.pmid: 15843919
references.citation: J Mol Biol. 1987 Aug 5;196(3):657-75
references.pmid: 3681971
references.citation: Science. 2001 Feb 9;291(5506):1043-7
references.pmid: 11161216
references.citation: Nature. 2004 Jun 10;429(6992):671-5
references.pmid: 15141227
references.citation: Neuron. 2003 Oct 9;40(2):265-76
references.pmid: 14556708
references.citation: Nature. 2001 Sep 13;413(6852):203-10
references.pmid: 11557989
references.citation: Cell. 2003 Feb 7;112(3):293-301
references.pmid: 12581520
references.citation: Curr Opin Struct Biol. 2008 Aug;18(4):477-83
references.pmid: 18555680
references.citation: Methods Enzymol. 1995;259:427-52
references.pmid: 8538465
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Mol Cell. 2002 Jan;9(1):163-73
references.pmid: 11804595
references.citation: Nature. 2003 Dec 4;426(6966):517-24
references.pmid: 14654832
references.citation: Cell. 2003 Jul 25;114(2):191-200
references.pmid: 12887921
references.citation: Adv Protein Chem. 2005;70:37-78
references.pmid: 15837513
references.citation: Annu Rev Physiol. 2002;64:19-46
references.pmid: 11826262
references.citation: Science. 2000 Jul 7;289(5476):123-7
references.pmid: 10884227
references.citation: Nature. 2002 Mar 7;416(6876):52-8
references.pmid: 11882888
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Mar;60(Pt 3):432-8
references.pmid: 14993666
references.citation: Methods Enzymol. 2003;374:22-37
references.pmid: 14696367
references.citation: J Biol Chem. 1996 Feb 23;271(8):3995-4001
references.pmid: 8626731
references.citation: Trends Cardiovasc Med. 2003 Feb;13(2):52-6
references.pmid: 12586439
references.citation: Sci STKE. 2004 Oct 05;2004(253):re15
references.pmid: 15467096
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61
references.pmid: 10089316
references.citation: Cell. 2003 Dec 26;115(7):863-77
references.pmid: 14697204
references.citation: Annu Rev Biochem. 2007;76:387-417
references.pmid: 17579562
references.citation: Science. 2002 Jan 18;295(5554):496-9
references.pmid: 11799244
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2894-9
references.pmid: 14976260
references.citation: Trends Pharmacol Sci. 2004 Dec;25(12):633-9
references.pmid: 15530641
references.citation: Gastroenterology. 2005 Nov;129(5):1504-17
references.pmid: 16285951
references.citation: J Biol Chem. 2006 Dec 15;281(50):38748-56
references.pmid: 17060318
references.citation: Nat Struct Mol Biol. 2006 Nov;13(11):987-95
references.pmid: 17057713
references.citation: J Struct Biol. 2002 Jan-Feb;137(1-2):54-64
references.pmid: 12064933
references.citation: Protein Expr Purif. 2005 May;41(1):207-34
references.pmid: 15915565
references.citation: Nat Struct Biol. 1999 May;6(5):458-63
references.pmid: 10331874
references.citation: Cell. 2002 Mar 8;108(5):595-8
references.pmid: 11893331