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<table><tr><td colspan='2'>[[6hts]] is a 19 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6etx 6etx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HTS FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6hts]] is a 19 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6etx 6etx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HTS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6HTS FirstGlance]. <br>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr>
6hts is a 19 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 6etx. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[INO80_HUMAN] DNA helicase and probable main scaffold component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair; according to PubMed:20687897 the contribution to DNA double-strand break repair appears to be largely indirect through transcriptional regulation. Recruited by YY1 to YY1-activated genes, where it acts as an essential coactivator. Binds DNA. In vitro, has double-stranded DNA-dependent ATPase activity. Involved in UV-damage excision repair, DNA replication and chromosome segregation during normal cell division cycle.[1][2][3][4][5][6][7] [IN80B_HUMAN] Induces growth and cell cycle arrests at the G1 phase of the cell cycle.[8] Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.[9] [RUVB2_HUMAN] Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity.[10] Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.[11] Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.[12] Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. May also inhibit the transcriptional activity of ATF2.[13] [H2B1J_HUMAN] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[14][15][16] Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.[17][18][19] [RUVB1_HUMAN] Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity.[20][21][22][23][24] Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.[25][26][27][28][29] Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.[30][31][32][33][34] Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex. Essential for cell proliferation.[35][36][37][38][39] May be able to bind plasminogen at cell surface and enhance plasminogen activation.[40][41][42][43][44] [ARP5_HUMAN] Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Involved in DNA double-strand break repair and UV-damage excision repair.[45][46]
Publication Abstract from PubMed
Access to DNA within nucleosomes is required for a variety of processes in cells including transcription, replication and repair. Consequently, cells encode multiple systems that remodel nucleosomes. These complexes can be simple, involving one or a few protein subunits, or more complicated multi-subunit machines (1) . Biochemical studies(2-4) have placed the motor domains of several chromatin remodellers in the superhelical location 2 region of the nucleosome. Structural studies of yeast Chd1 and Snf2-a subunit in the complex with the capacity to remodel the structure of chromatin (RSC)-in complex with nucleosomes(5-7) have provided insights into the basic mechanism of nucleosome sliding performed by these complexes. However, how larger, multi-subunit remodelling complexes such as INO80 interact with nucleosomes and how remodellers carry out functions such as nucleosome sliding (8) , histone exchange (9) and nucleosome spacing(10-12) remain poorly understood. Although some remodellers work as monomers (13) , others work as highly cooperative dimers(11, 14, 15). Here we present the structure of the human INO80 chromatin remodeller with a bound nucleosome, which reveals that INO80 interacts with nucleosomes in a previously undescribed manner: the motor domains are located on the DNA at the entry point to the nucleosome, rather than at superhelical location 2. The ARP5-IES6 module of INO80 makes additional contacts on the opposite side of the nucleosome. This arrangement enables the histone H3 tails of the nucleosome to have a role in the regulation of the activities of the INO80 motor domain-unlike in other characterized remodellers, for which H4 tails have been shown to regulate the motor domains.
Structure and regulation of the human INO80-nucleosome complex.,Ayala R, Willhoft O, Aramayo RJ, Wilkinson M, McCormack EA, Ocloo L, Wigley DB, Zhang X Nature. 2018 Apr;556(7701):391-395. doi: 10.1038/s41586-018-0021-6. Epub 2018 Apr, 11. PMID:29643506[47]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑ Jin J, Cai Y, Yao T, Gottschalk AJ, Florens L, Swanson SK, Gutierrez JL, Coleman MK, Workman JL, Mushegian A, Washburn MP, Conaway RC, Conaway JW. A mammalian chromatin remodeling complex with similarities to the yeast INO80 complex. J Biol Chem. 2005 Dec 16;280(50):41207-12. Epub 2005 Oct 17. PMID:16230350 doi:http://dx.doi.org/M509128200
↑ Bakshi R, Mehta AK, Sharma R, Maiti S, Pasha S, Brahmachari V. Characterization of a human SWI2/SNF2 like protein hINO80: demonstration of catalytic and DNA binding activity. Biochem Biophys Res Commun. 2006 Jan 6;339(1):313-20. Epub 2005 Nov 15. PMID:16298340 doi:http://dx.doi.org/S0006-291X(05)02466-6
↑ Cai Y, Jin J, Yao T, Gottschalk AJ, Swanson SK, Wu S, Shi Y, Washburn MP, Florens L, Conaway RC, Conaway JW. YY1 functions with INO80 to activate transcription. Nat Struct Mol Biol. 2007 Sep;14(9):872-4. Epub 2007 Aug 26. PMID:17721549 doi:http://dx.doi.org/nsmb1276
↑ Hur SK, Park EJ, Han JE, Kim YA, Kim JD, Kang D, Kwon J. Roles of human INO80 chromatin remodeling enzyme in DNA replication and chromosome segregation suppress genome instability. Cell Mol Life Sci. 2010 Jul;67(13):2283-96. doi: 10.1007/s00018-010-0337-3. Epub , 2010 Mar 17. PMID:20237820 doi:http://dx.doi.org/10.1007/s00018-010-0337-3
↑ Park EJ, Hur SK, Kwon J. Human INO80 chromatin-remodelling complex contributes to DNA double-strand break repair via the expression of Rad54B and XRCC3 genes. Biochem J. 2010 Oct 15;431(2):179-87. doi: 10.1042/BJ20100988. PMID:20687897 doi:http://dx.doi.org/10.1042/BJ20100988
↑ Jiang Y, Wang X, Bao S, Guo R, Johnson DG, Shen X, Li L. INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17274-9. doi:, 10.1073/pnas.1008388107. Epub 2010 Sep 20. PMID:20855601 doi:http://dx.doi.org/10.1073/pnas.1008388107
↑ Chen L, Cai Y, Jin J, Florens L, Swanson SK, Washburn MP, Conaway JW, Conaway RC. Subunit organization of the human INO80 chromatin remodeling complex: an evolutionarily conserved core complex catalyzes ATP-dependent nucleosome remodeling. J Biol Chem. 2011 Apr 1;286(13):11283-9. doi: 10.1074/jbc.M111.222505. Epub 2011 , Feb 8. PMID:21303910 doi:http://dx.doi.org/10.1074/jbc.M111.222505
↑ Kuroda TS, Maita H, Tabata T, Taira T, Kitaura H, Ariga H, Iguchi-Ariga SM. A novel nucleolar protein, PAPA-1, induces growth arrest as a result of cell cycle arrest at the G1 phase. Gene. 2004 Sep 29;340(1):83-98. doi: 10.1016/j.gene.2004.05.025. PMID:15556297 doi:http://dx.doi.org/10.1016/j.gene.2004.05.025
↑ Kuroda TS, Maita H, Tabata T, Taira T, Kitaura H, Ariga H, Iguchi-Ariga SM. A novel nucleolar protein, PAPA-1, induces growth arrest as a result of cell cycle arrest at the G1 phase. Gene. 2004 Sep 29;340(1):83-98. doi: 10.1016/j.gene.2004.05.025. PMID:15556297 doi:http://dx.doi.org/10.1016/j.gene.2004.05.025
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Kim HS, Cho JH, Park HW, Yoon H, Kim MS, Kim SC. Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol. 2002 Mar 1;168(5):2356-64. PMID:11859126
↑ Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides. 2003 Apr;24(4):523-30. PMID:12860195
↑ Howell SJ, Wilk D, Yadav SP, Bevins CL. Antimicrobial polypeptides of the human colonic epithelium. Peptides. 2003 Nov;24(11):1763-70. PMID:15019208 doi:10.1016/j.peptides.2003.07.028
↑ Kim HS, Cho JH, Park HW, Yoon H, Kim MS, Kim SC. Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol. 2002 Mar 1;168(5):2356-64. PMID:11859126
↑ Tollin M, Bergman P, Svenberg T, Jornvall H, Gudmundsson GH, Agerberth B. Antimicrobial peptides in the first line defence of human colon mucosa. Peptides. 2003 Apr;24(4):523-30. PMID:12860195
↑ Howell SJ, Wilk D, Yadav SP, Bevins CL. Antimicrobial polypeptides of the human colonic epithelium. Peptides. 2003 Nov;24(11):1763-70. PMID:15019208 doi:10.1016/j.peptides.2003.07.028
↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Hawley SB, Tamura T, Miles LA. Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J Biol Chem. 2001 Jan 5;276(1):179-86. PMID:11027681 doi:http://dx.doi.org/10.1074/jbc.M004919200
↑ Gartner W, Rossbacher J, Zierhut B, Daneva T, Base W, Weissel M, Waldhausl W, Pasternack MS, Wagner L. The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis. Cell Motil Cytoskeleton. 2003 Oct;56(2):79-93. PMID:14506706 doi:http://dx.doi.org/10.1002/cm.10136
↑ Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R, Pradel J. Pontin52 and reptin52 function as antagonistic regulators of beta-catenin signalling activity. EMBO J. 2000 Nov 15;19(22):6121-30. PMID:11080158 doi:http://dx.doi.org/10.1093/emboj/19.22.6121
↑ Feng Y, Lee N, Fearon ER. TIP49 regulates beta-catenin-mediated neoplastic transformation and T-cell factor target gene induction via effects on chromatin remodeling. Cancer Res. 2003 Dec 15;63(24):8726-34. PMID:14695187
↑ Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004 Mar;24(5):1884-96. PMID:14966270
↑ Kitayama K, Kamo M, Oma Y, Matsuda R, Uchida T, Ikura T, Tashiro S, Ohyama T, Winsor B, Harata M. The human actin-related protein hArp5: nucleo-cytoplasmic shuttling and involvement in DNA repair. Exp Cell Res. 2009 Jan 15;315(2):206-17. doi: 10.1016/j.yexcr.2008.10.028. Epub, 2008 Nov 5. PMID:19014934 doi:http://dx.doi.org/10.1016/j.yexcr.2008.10.028
↑ Jiang Y, Wang X, Bao S, Guo R, Johnson DG, Shen X, Li L. INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17274-9. doi:, 10.1073/pnas.1008388107. Epub 2010 Sep 20. PMID:20855601 doi:http://dx.doi.org/10.1073/pnas.1008388107
↑ Ayala R, Willhoft O, Aramayo RJ, Wilkinson M, McCormack EA, Ocloo L, Wigley DB, Zhang X. Structure and regulation of the human INO80-nucleosome complex. Nature. 2018 Apr;556(7701):391-395. doi: 10.1038/s41586-018-0021-6. Epub 2018 Apr, 11. PMID:29643506 doi:http://dx.doi.org/10.1038/s41586-018-0021-6
