title: Structure of an actin-related subcomplex of the SWI/SNF chromatin remodeler.
abstract: The packaging of DNA into nucleosomal structures limits access for templated processes such as transcription and DNA repair. The repositioning or ejection of nucleosomes is therefore critically important for regulated events, including gene expression. This activity is provided by chromatin remodeling complexes, or remodelers, which are typically large, multisubunit complexes that use an ATPase subunit to translocate the DNA. Many remodelers contain pairs or multimers of actin-related proteins (ARPs) that contact the helicase-SANT-associated (HSA) domain within the catalytic ATPase subunit and are thought to regulate ATPase activity. Here, we determined the structure of a four-protein subcomplex within the SWI/SNF remodeler that comprises the Snf2 HSA domain, Arp7, Arp9, and repressor of Ty1 transposition, gene 102 (Rtt102). Surprisingly, unlike characterized actin-actin associations, the two ARPs pack like spoons and straddle the HSA domain, which forms a 92-Å-long helix. The ARP-HSA interactions are reminiscent of contacts between actin and many binding partners and are quite different from those in the Arp2/3 complex. Rtt102 wraps around one side of the complex in a highly extended conformation that contacts both ARPs and therefore stabilizes the complex, yet functions to reduce by ∼2.4-fold the remodeling and ATPase activity of complexes containing the Snf2 ATPase domain. Thus, our structure provides a foundation for developing models of remodeler function, including mechanisms of coupling between ARPs and the ATPase translocation activity.
authors: Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors: Heidi L
authors: HL
authors: Schubert
authors: Jacqueline
authors: J
authors: Wittmeyer
authors: Margaret M
authors: MM
authors: Kasten
authors: Kaede
authors: K
authors: Hinata
authors: David C
authors: DC
authors: Rawling
authors: Annie
authors: A
authors: Héroux
authors: Bradley R
authors: BR
authors: Cairns
authors: Christopher P
authors: CP
authors: Hill
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004331:Drosophila melanogaster / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000199:Actins; D002868:Chromosomal Proteins, Non-Histone; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D009707:Nucleosomes; C445179:SWI-SNF-B chromatin-remodeling complex; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
references: Mol Biol Cell. 2005 Dec;16(12):5736-48
references: 16195354
references: Nature. 1990 Sep 6;347(6288):37-44
references: 2395459
references: Mol Cell. 1998 Nov;2(5):639-51
references: 9844636
references: EMBO J. 2011 Jun 1;30(11):2153-66
references: 21499228
references: Nucleic Acids Res. 2012 Nov;40(21):11036-46
references: 22977180
references: Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
references: 20383002
references: Cell. 1998 Nov 25;95(5):717-28
references: 9845373
references: Methods Enzymol. 2003;374:300-21
references: 14696379
references: EMBO J. 2004 Mar 24;23(6):1348-59
references: 15014446
references: EMBO J. 2011 May 06;30(12):2364-72
references: 21552204
references: Protein Expr Purif. 2005 May;41(1):207-34
references: 15915565
references: Genes Dev. 2005 Jul 15;19(14):1656-61
references: 16024655
references: Mol Cell. 2004 Nov 5;16(3):465-77
references: 15525518
references: Annu Rev Biochem. 2002;71:755-81
references: 12045110
references: Genes Dev. 2002 Apr 1;16(7):806-19
references: 11937489
references: Nature. 2009 Jan 22;457(7228):441-5
references: 19158791
references: Nature. 1993 Aug 19;364(6439):685-92
references: 8395021
references: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references: 15299926
references: EMBO J. 2012 Jan 4;31(1):236-47
references: 21934650
references: Nat Struct Mol Biol. 2008 May;15(5):469-76
references: 18408732
references: J Mol Biol. 1994 Feb 25;236(3):869-86
references: 8114100
references: EMBO J. 2003 Jun 16;22(12):3175-87
references: 12805231
references: Science. 2001 Nov 23;294(5547):1679-84
references: 11721045
references: Mol Cell Biol. 2004 Sep;24(18):8227-35
references: 15340082
references: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5760-5
references: 12732734
references: Annu Rev Biochem. 2009;78:273-304
references: 19355820
references: Mol Cell. 2002 Mar;9(3):563-73
references: 11931764
references: Mol Cell Biol. 2006 Jul;26(13):4920-33
references: 16782880
references: Mol Cell. 2001 Apr;7(4):741-51
references: 11336698
references: Cell. 1998 Nov 25;95(5):625-36
references: 9845365
references: Cell. 2004 May 28;117(5):611-23
references: 15163409
references: Annu Rev Biophys. 2011;40:169-86
references: 21314430
references: J Mol Biol. 2007 Sep 21;372(3):774-97
references: 17681537
references: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
references: 20124702
references: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3364-9
references: 10725359
references: Genes Dev. 2002 Aug 15;16(16):2120-34
references: 12183366
references: Nat Struct Mol Biol. 2005 Sep;12(9):747-55
references: 16086025
references: Mol Cell. 2000 Jun;5(6):927-37
references: 10911987
references: Mol Cell. 2003 Jul;12(1):147-55
references: 12887900
references: FASEB J. 1995 Feb;9(2):167-74
references: 7781919
references: Mol Cell. 2007 May 11;26(3):449-57
references: 17499050
references: J Cell Biol. 2008 Mar 10;180(5):887-95
references: 18316411
references: Nat Struct Mol Biol. 2007 Jun;14(6):540-7
references: 17496903
references: Methods Enzymol. 2004;377:322-43
references: 14979035