8ieg

From Proteopedia

(Difference between revisions)

Revision as of 06:24, 6 September 2023

Bre1(mRBD-RING)/Rad6-Ub/nucleosome complex

Structural highlights

8ieg is a 13 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.44Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BRE1_YEAST E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H2B to form H2BK123ub1 in association with the E2 enzyme RAD6/UBC2. H2BK123ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. It thereby plays a central role in histone code and gene regulation. Also modulates the formation of double-strand breaks during meiosis.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Histone H2B monoubiquitylation plays essential roles in chromatin-based transcriptional processes. A RING-type E3 ligase (yeast Bre1 or human RNF20/RNF40) and an E2 ubiquitin-conjugating enzyme (yeast Rad6 or human hRAD6A), together, precisely deposit ubiquitin on H2B K123 in yeast or K120 in humans. Here, we developed a chemical trapping strategy and successfully captured the transient structures of Bre1- or RNF20/RNF40-mediated ubiquitin transfer from Rad6 or hRAD6A to nucleosomal H2B. Our structures show that Bre1 and RNF40 directly bind nucleosomal DNA, exhibiting a conserved E3/E2/nucleosome interaction pattern from yeast to humans for H2B monoubiquitylation. We also find an uncanonical non-hydrophobic contact in the Bre1 RING-Rad6 interface, which positions Rad6 directly above the target H2B lysine residue. Our study provides mechanistic insights into the site-specific monoubiquitylation of H2B, reveals a critical role of nucleosomal DNA in mediating E3 ligase recognition, and provides a framework for understanding the cancer-driving mutations of RNF20/RNF40.

Mechanistic insights into nucleosomal H2B monoubiquitylation mediated by yeast Bre1-Rad6 and its human homolog RNF20/RNF40-hRAD6A.,Deng Z, Ai H, Sun M, Tong Z, Du Y, Qu Q, Zhang L, Xu Z, Tao S, Shi Q, Li JB, Pan M, Liu L Mol Cell. 2023 Aug 17:S1097-2765(23)00607-X. doi: 10.1016/j.molcel.2023.08.001. PMID:37633270^[6]

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

References

↑ Hwang WW, Venkatasubrahmanyam S, Ianculescu AG, Tong A, Boone C, Madhani HD. A conserved RING finger protein required for histone H2B monoubiquitination and cell size control. Mol Cell. 2003 Jan;11(1):261-6. PMID:12535538
↑ Wood A, Krogan NJ, Dover J, Schneider J, Heidt J, Boateng MA, Dean K, Golshani A, Zhang Y, Greenblatt JF, Johnston M, Shilatifard A. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol Cell. 2003 Jan;11(1):267-74. PMID:12535539
↑ Wood A, Schneider J, Dover J, Johnston M, Shilatifard A. The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and Dot1p. J Biol Chem. 2003 Sep 12;278(37):34739-42. Epub 2003 Jul 21. PMID:12876294 doi:http://dx.doi.org/10.1074/jbc.C300269200
↑ Yamashita K, Shinohara M, Shinohara A. Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11380-5. Epub 2004 Jul 27. PMID:15280549 doi:10.1073/pnas.0400078101
↑ Xiao T, Kao CF, Krogan NJ, Sun ZW, Greenblatt JF, Osley MA, Strahl BD. Histone H2B ubiquitylation is associated with elongating RNA polymerase II. Mol Cell Biol. 2005 Jan;25(2):637-51. PMID:15632065 doi:25/2/637
↑ Deng Z, Ai H, Sun M, Tong Z, Du Y, Qu Q, Zhang L, Xu Z, Tao S, Shi Q, Li JB, Pan M, Liu L. Mechanistic insights into nucleosomal H2B monoubiquitylation mediated by yeast Bre1-Rad6 and its human homolog RNF20/RNF40-hRAD6A. Mol Cell. 2023 Aug 17:S1097-2765(23)00607-X. PMID:37633270 doi:10.1016/j.molcel.2023.08.001

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/8ieg"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8ieg is ON HOLD  until Paper Publication
+==Bre1(mRBD-RING)/Rad6-Ub/nucleosome complex==
+<StructureSection load='8ieg' size='340' side='right'caption='[[8ieg]], [[Resolution|resolution]] 3.44&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8ieg]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IEG FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.44&#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=8ieg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ieg OCA], [https://pdbe.org/8ieg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ieg RCSB], [https://www.ebi.ac.uk/pdbsum/8ieg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ieg ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/BRE1_YEAST BRE1_YEAST] E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H2B to form H2BK123ub1 in association with the E2 enzyme RAD6/UBC2. H2BK123ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. It thereby plays a central role in histone code and gene regulation. Also modulates the formation of double-strand breaks during meiosis.<ref>PMID:12535538</ref> <ref>PMID:12535539</ref> <ref>PMID:12876294</ref> <ref>PMID:15280549</ref> <ref>PMID:15632065</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Histone H2B monoubiquitylation plays essential roles in chromatin-based transcriptional processes. A RING-type E3 ligase (yeast Bre1 or human RNF20/RNF40) and an E2 ubiquitin-conjugating enzyme (yeast Rad6 or human hRAD6A), together, precisely deposit ubiquitin on H2B K123 in yeast or K120 in humans. Here, we developed a chemical trapping strategy and successfully captured the transient structures of Bre1- or RNF20/RNF40-mediated ubiquitin transfer from Rad6 or hRAD6A to nucleosomal H2B. Our structures show that Bre1 and RNF40 directly bind nucleosomal DNA, exhibiting a conserved E3/E2/nucleosome interaction pattern from yeast to humans for H2B monoubiquitylation. We also find an uncanonical non-hydrophobic contact in the Bre1 RING-Rad6 interface, which positions Rad6 directly above the target H2B lysine residue. Our study provides mechanistic insights into the site-specific monoubiquitylation of H2B, reveals a critical role of nucleosomal DNA in mediating E3 ligase recognition, and provides a framework for understanding the cancer-driving mutations of RNF20/RNF40.
-Authors:
+Mechanistic insights into nucleosomal H2B monoubiquitylation mediated by yeast Bre1-Rad6 and its human homolog RNF20/RNF40-hRAD6A.,Deng Z, Ai H, Sun M, Tong Z, Du Y, Qu Q, Zhang L, Xu Z, Tao S, Shi Q, Li JB, Pan M, Liu L Mol Cell. 2023 Aug 17:S1097-2765(23)00607-X. doi: 10.1016/j.molcel.2023.08.001. PMID:37633270<ref>PMID:37633270</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8ieg" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae S288C]]
+[[Category: Ai H]]
+[[Category: Deng Z]]
+[[Category: Liu L]]
+[[Category: Pan M]]

8ieg

From Proteopedia

Revision as of 06:24, 6 September 2023

Bre1(mRBD-RING)/Rad6-Ub/nucleosome complex

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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