4b86

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the MSL1-MSL2 complex (3.5A)

Structural highlights

4b86 is a 12 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 3.5Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MSL1_HUMAN Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at 'Lys-16' (H4K16ac) which is implicated in the formation of higher-order chromatin structure. Greatly enhances MSL2 E3 ubiquitin ligase activity, promoting monoubiquitination of histone H2B at 'Lys-34' (H2BK34Ub). This modification in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1. In the MSL complex, acts as a scaffold to tether MSL3 and KAT8 together for enzymatic activity regulation.^[1] ^[2] ^[3]

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^[4]

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

References

↑ Smith ER, Cayrou C, Huang R, Lane WS, Cote J, Lucchesi JC. A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16. Mol Cell Biol. 2005 Nov;25(21):9175-88. PMID:16227571 doi:10.1128/MCB.25.21.9175-9188.2005
↑ Wu L, Zee BM, Wang Y, Garcia BA, Dou Y. The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation. Mol Cell. 2011 Jul 8;43(1):132-44. doi: 10.1016/j.molcel.2011.05.015. PMID:21726816 doi:http://dx.doi.org/10.1016/j.molcel.2011.05.015
↑ Huang J, Wan B, Wu L, Yang Y, Dou Y, Lei M. Structural insight into the regulation of MOF in the male-specific lethal complex and the non-specific lethal complex. Cell Res. 2012 Jun;22(6):1078-81. doi: 10.1038/cr.2012.72. Epub 2012 May 1. PMID:22547026 doi:10.1038/cr.2012.72
↑ Hallacli E, Lipp M, Georgiev P, Spielman C, Cusack S, Akhtar A, Kadlec J. Msl1-mediated dimerization of the dosage compensation complex is essential for male X-chromosome regulation in Drosophila. Mol Cell. 2012 Nov 30;48(4):587-600. doi: 10.1016/j.molcel.2012.09.014. Epub 2012, Oct 18. PMID:23084835 doi:http://dx.doi.org/10.1016/j.molcel.2012.09.014

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4b86"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4b86 is ON HOLD  until sometime in the future
+==Crystal structure of the MSL1-MSL2 complex (3.5A)==
+<StructureSection load='4b86' size='340' side='right'caption='[[4b86]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4b86]] is a 12 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=4B86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B86 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]] 3.5&#8491;</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=4b86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b86 OCA], [https://pdbe.org/4b86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b86 RCSB], [https://www.ebi.ac.uk/pdbsum/4b86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b86 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MSL1_HUMAN MSL1_HUMAN] Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at 'Lys-16' (H4K16ac) which is implicated in the formation of higher-order chromatin structure. Greatly enhances MSL2 E3 ubiquitin ligase activity, promoting monoubiquitination of histone H2B at 'Lys-34' (H2BK34Ub). This modification in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1. In the MSL complex, acts as a scaffold to tether MSL3 and KAT8 together for enzymatic activity regulation.<ref>PMID:16227571</ref> <ref>PMID:21726816</ref> <ref>PMID:22547026</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.
-Authors: Hallacli, E., Lipp, M., Georgiev, P., Spielman, C., Cusack, S., Akhtar, A., Kadlec, J.
+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>
-Description: Crystal structure of the MSL1-MSL2 complex
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4b86" 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]]

4b86

From Proteopedia

Current revision

Crystal structure of the MSL1-MSL2 complex (3.5A)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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