4b7y: Difference between revisions
New page: '''Unreleased structure''' The entry 4b7y is ON HOLD Authors: Hallacli, E., Lipp, M., Georgiev, P., Spielman, C., Cusack, S., Akhtar, A., Kadlec, J. Description: Crystal structure of t... |
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The | ==Crystal structure of the MSL1-MSL2 complex== | ||
<StructureSection load='4b7y' size='340' side='right'caption='[[4b7y]], [[Resolution|resolution]] 3.25Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4b7y]] is a 4 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=4B7Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B7Y FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.25Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4b7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b7y OCA], [https://pdbe.org/4b7y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b7y RCSB], [https://www.ebi.ac.uk/pdbsum/4b7y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b7y ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MSL2_HUMAN MSL2_HUMAN] Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at lysine 16 which is implicated in the formation of higher-order chromatin structure. Acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. This activity is greatly enhanced by heterodimerization with MSL1. H2B ubiquitination in turn stimulates histine H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1.<ref>PMID:21726816</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Male-Specific Lethal (MSL) complex regulates dosage compensation of the male X chromosome in Drosophila. Here, we report the crystal structure of its MSL1/MSL2 core, where two MSL2 subunits bind to a dimer formed by two molecules of MSL1. Analysis of structure-based mutants revealed that MSL2 can only interact with the MSL1 dimer, but MSL1 dimerization is MSL2 independent. We show that Msl1 is a substrate for Msl2 E3 ubiquitin ligase activity. ChIP experiments revealed that Msl1 dimerization is essential for targeting and spreading of the MSL complex on X-linked genes; however, Msl1 binding to promoters of male and female cells is independent of the dimer status and other MSL proteins. Finally, we show that loss of Msl1 dimerization leads to male-specific lethality. We propose that Msl1-mediated dimerization of the entire MSL complex is required for Msl2 binding, X chromosome recognition, and spreading along the X chromosome. | |||
Msl1-mediated dimerization of the dosage compensation complex is essential for male X-chromosome regulation in Drosophila.,Hallacli E, Lipp M, Georgiev P, Spielman C, Cusack S, Akhtar A, Kadlec J Mol Cell. 2012 Nov 30;48(4):587-600. doi: 10.1016/j.molcel.2012.09.014. Epub 2012, Oct 18. PMID:23084835<ref>PMID:23084835</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4b7y" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Akhtar A]] | |||
[[Category: Cusack S]] | |||
[[Category: Georgiev P]] | |||
[[Category: Hallacli E]] | |||
[[Category: Kadlec J]] | |||
[[Category: Lipp M]] | |||
[[Category: Spielman C]] | |||
Latest revision as of 14:45, 20 December 2023
Crystal structure of the MSL1-MSL2 complexCrystal structure of the MSL1-MSL2 complex
Structural highlights
FunctionMSL2_HUMAN Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at lysine 16 which is implicated in the formation of higher-order chromatin structure. Acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. This activity is greatly enhanced by heterodimerization with MSL1. H2B ubiquitination in turn stimulates histine H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1.[1] Publication Abstract from PubMedThe Male-Specific Lethal (MSL) complex regulates dosage compensation of the male X chromosome in Drosophila. Here, we report the crystal structure of its MSL1/MSL2 core, where two MSL2 subunits bind to a dimer formed by two molecules of MSL1. Analysis of structure-based mutants revealed that MSL2 can only interact with the MSL1 dimer, but MSL1 dimerization is MSL2 independent. We show that Msl1 is a substrate for Msl2 E3 ubiquitin ligase activity. ChIP experiments revealed that Msl1 dimerization is essential for targeting and spreading of the MSL complex on X-linked genes; however, Msl1 binding to promoters of male and female cells is independent of the dimer status and other MSL proteins. Finally, we show that loss of Msl1 dimerization leads to male-specific lethality. We propose that Msl1-mediated dimerization of the entire MSL complex is required for Msl2 binding, X chromosome recognition, and spreading along the X chromosome. Msl1-mediated dimerization of the dosage compensation complex is essential for male X-chromosome regulation in Drosophila.,Hallacli E, Lipp M, Georgiev P, Spielman C, Cusack S, Akhtar A, Kadlec J Mol Cell. 2012 Nov 30;48(4):587-600. doi: 10.1016/j.molcel.2012.09.014. Epub 2012, Oct 18. PMID:23084835[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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