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3iif

From Proteopedia

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Current revision

Crystal structure of the macro domain of human histone macroH2A1.1 in complex with ADP-ribose (form B)

Structural highlights

3iif is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

H2AY_HUMAN Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. 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. Involved in stable X chromosome inactivation. Inhibits the binding of transcription factors and interferes with the activity of remodeling SWI/SNF complexes. Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin. In addition, isoform 1, but not isoform 2, binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation.^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Poly-ADP-ribosylation is a post-translational modification catalyzed by PARP enzymes with roles in transcription and chromatin biology. Here we show that distinct macrodomains, including those of histone macroH2A1.1, are recruited to sites of PARP1 activation induced by laser-generated DNA damage. Chemical PARP1 inhibitors, PARP1 knockdown and mutation of ADP-ribose-binding residues in macroH2A1.1 abrogate macrodomain recruitment. Notably, histone macroH2A1.1 senses PARP1 activation, transiently compacts chromatin, reduces the recruitment of DNA damage factor Ku70-Ku80 and alters gamma-H2AX patterns, whereas the splice variant macroH2A1.2, which is deficient in poly-ADP-ribose binding, does not mediate chromatin rearrangements upon PARP1 activation. The structure of the macroH2A1.1 macrodomain in complex with ADP-ribose establishes a poly-ADP-ribose cap-binding function and reveals conformational changes in the macrodomain upon ligand binding. We thus identify macrodomains as modules that directly sense PARP activation in vivo and establish macroH2A histones as dynamic regulators of chromatin plasticity.

A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation.,Timinszky G, Till S, Hassa PO, Hothorn M, Kustatscher G, Nijmeijer B, Colombelli J, Altmeyer M, Stelzer EH, Scheffzek K, Hottiger MO, Ladurner AG Nat Struct Mol Biol. 2009 Sep;16(9):923-9. Epub 2009 Aug 13. PMID:19680243^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Angelov D, Molla A, Perche PY, Hans F, Cote J, Khochbin S, Bouvet P, Dimitrov S. The histone variant macroH2A interferes with transcription factor binding and SWI/SNF nucleosome remodeling. Mol Cell. 2003 Apr;11(4):1033-41. PMID:12718888
↑ Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell. 2005 Jan;8(1):19-30. PMID:15621527 doi:S1534580704004083
↑ Hernandez-Munoz I, Lund AH, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, Nusinow DA, Panning B, Marahrens Y, van Lohuizen M. Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7635-40. Epub 2005 May 16. PMID:15897469 doi:0408918102
↑ Doyen CM, An W, Angelov D, Bondarenko V, Mietton F, Studitsky VM, Hamiche A, Roeder RG, Bouvet P, Dimitrov S. Mechanism of polymerase II transcription repression by the histone variant macroH2A. Mol Cell Biol. 2006 Feb;26(3):1156-64. PMID:16428466 doi:10.1128/MCB.26.3.1156-1164.2006
↑ Chakravarthy S, Gundimella SK, Caron C, Perche PY, Pehrson JR, Khochbin S, Luger K. Structural characterization of the histone variant macroH2A. Mol Cell Biol. 2005 Sep;25(17):7616-24. PMID:16107708 doi:http://dx.doi.org/25/17/7616
↑ Timinszky G, Till S, Hassa PO, Hothorn M, Kustatscher G, Nijmeijer B, Colombelli J, Altmeyer M, Stelzer EH, Scheffzek K, Hottiger MO, Ladurner AG. A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation. Nat Struct Mol Biol. 2009 Sep;16(9):923-9. Epub 2009 Aug 13. PMID:19680243 doi:10.1038/nsmb.1664

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3iif"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the macro domain of human histone macroH2A1.1 in complex with ADP-ribose (form B)==
-<StructureSection load='3iif' size='340' side='right' caption='[[3iif]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='3iif' size='340' side='right'caption='[[3iif]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3iif]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IIF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3iif]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IIF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IIF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zr3|1zr3]], [[2fxk|2fxk]], [[3iid|3iid]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">H2AFY, MACROH2A1, macroH2A1.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3iif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iif OCA], [https://pdbe.org/3iif PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iif RCSB], [https://www.ebi.ac.uk/pdbsum/3iif PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iif ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3iif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iif OCA], [http://pdbe.org/3iif PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3iif RCSB], [http://www.ebi.ac.uk/pdbsum/3iif PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3iif ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/H2AY_HUMAN H2AY_HUMAN]] Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. 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. Involved in stable X chromosome inactivation. Inhibits the binding of transcription factors and interferes with the activity of remodeling SWI/SNF complexes. Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin. In addition, isoform 1, but not isoform 2, binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation.<ref>PMID:12718888</ref> <ref>PMID:15621527</ref> <ref>PMID:15897469</ref> <ref>PMID:16428466</ref> <ref>PMID:16107708</ref>
+[https://www.uniprot.org/uniprot/H2AY_HUMAN H2AY_HUMAN] Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. 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. Involved in stable X chromosome inactivation. Inhibits the binding of transcription factors and interferes with the activity of remodeling SWI/SNF complexes. Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin. In addition, isoform 1, but not isoform 2, binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation.<ref>PMID:12718888</ref> <ref>PMID:15621527</ref> <ref>PMID:15897469</ref> <ref>PMID:16428466</ref> <ref>PMID:16107708</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 31: @@
 ==See Also==
-*[[Histone|Histone]]
+*[[Histone 3D structures|Histone 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Bortfeld, M]]
+[[Category: Large Structures]]
-[[Category: Hothorn, M]]
+[[Category: Bortfeld M]]
-[[Category: Ladurner, A G]]
+[[Category: Hothorn M]]
-[[Category: Scheffzek, K]]
+[[Category: Ladurner AG]]
-[[Category: Chromatin]]
+[[Category: Scheffzek K]]
-[[Category: Chromatin regulator]]
-[[Category: Chromosomal protein]]
-[[Category: Dna-binding]]
-[[Category: Gene regulation]]
-[[Category: Histone]]
-[[Category: Isopeptide bond]]
-[[Category: Macro domain]]
-[[Category: Methylation]]
-[[Category: Nucleosome core]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]

3iif

From Proteopedia

Current revision

Crystal structure of the macro domain of human histone macroH2A1.1 in complex with ADP-ribose (form B)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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