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| - | [[Image:2i50.jpg|left|200px]]<br /><applet load="2i50" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="2i50" /> | |
| - | '''Solution Structure of Ubp-M Znf-UBP domain'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Solution Structure of Ubp-M Znf-UBP domain== |
| - | The BUZ/Znf-UBP domain is a distinct ubiquitin-binding module found in the, cytoplasmic deacetylase HDAC6, the E3 ubiquitin ligase BRAP2/IMP, and a, subfamily of deubiquitinating enzymes. Here, we report the solution, structure of the BUZ domain of Ubp-M, a ubiquitin-specific protease, and, its interaction with ubiquitin. Unlike the BUZ domain from isopeptidase T, (isoT) that contains a single zinc finger, the Ubp-M BUZ domain features, three zinc-binding sites consisting of 12 residues. These zinc ligands, form a pair of cross-braced ring fingers encapsulated within a third zinc, finger in the primary structure. In contrast to isoT, which can form an, N-terminal loop swapped dimer in the crystal state, the formation of, additional zinc fingers in the Ubp-M BUZ domain restricts its N-terminal, loop to intra-domain interactions. The ubiquitin-binding site of the Ubp-M, BUZ domain is mapped to the highly conserved, concave surface formed by, the alpha 3 helix and the central beta-sheet. We further show that this, site binds to the C-terminal tail of free ubiquitin, and corresponding, peptides display essentially the same binding affinities as full-length, ubiquitin does for the Ubp-M BUZ domain. However, modification of the, G76(Ub) carboxylate group either by a peptide or isopeptide bond abolishes, BUZ-domain interaction. The unique ubiquitin-recognition mode of the BUZ, domain family suggests that they may function as "sensors" of free, ubiquitin in cells to achieve regulatory roles in many aspects of, ubiquitin-dependent processes. | + | <StructureSection load='2i50' size='340' side='right'caption='[[2i50]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2i50]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I50 FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2i50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i50 OCA], [https://pdbe.org/2i50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i50 RCSB], [https://www.ebi.ac.uk/pdbsum/2i50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i50 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/UBP16_HUMAN UBP16_HUMAN] Note=A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/UBP16_HUMAN UBP16_HUMAN] Specifically deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-10' of histone H3, and is required for chromosome segregation when cells enter into mitosis. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.<ref>PMID:10077596</ref> <ref>PMID:11753566</ref> <ref>PMID:17914355</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i5/2i50_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2i50 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The BUZ/Znf-UBP domain is a distinct ubiquitin-binding module found in the cytoplasmic deacetylase HDAC6, the E3 ubiquitin ligase BRAP2/IMP, and a subfamily of deubiquitinating enzymes. Here, we report the solution structure of the BUZ domain of Ubp-M, a ubiquitin-specific protease, and its interaction with ubiquitin. Unlike the BUZ domain from isopeptidase T (isoT) that contains a single zinc finger, the Ubp-M BUZ domain features three zinc-binding sites consisting of 12 residues. These zinc ligands form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. In contrast to isoT, which can form an N-terminal loop swapped dimer in the crystal state, the formation of additional zinc fingers in the Ubp-M BUZ domain restricts its N-terminal loop to intra-domain interactions. The ubiquitin-binding site of the Ubp-M BUZ domain is mapped to the highly conserved, concave surface formed by the alpha 3 helix and the central beta-sheet. We further show that this site binds to the C-terminal tail of free ubiquitin, and corresponding peptides display essentially the same binding affinities as full-length ubiquitin does for the Ubp-M BUZ domain. However, modification of the G76(Ub) carboxylate group either by a peptide or isopeptide bond abolishes BUZ-domain interaction. The unique ubiquitin-recognition mode of the BUZ domain family suggests that they may function as "sensors" of free ubiquitin in cells to achieve regulatory roles in many aspects of ubiquitin-dependent processes. |
| | | | |
| - | ==About this Structure==
| + | Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin.,Pai MT, Tzeng SR, Kovacs JJ, Keaton MA, Li SS, Yao TP, Zhou P J Mol Biol. 2007 Jul 6;370(2):290-302. Epub 2007 Apr 12. PMID:17512543<ref>PMID:17512543</ref> |
| - | 2I50 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I50 OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin., Pai MT, Tzeng SR, Kovacs JJ, Keaton MA, Li SS, Yao TP, Zhou P, J Mol Biol. 2007 Jul 6;370(2):290-302. Epub 2007 Apr 12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17512543 17512543]
| + | </div> |
| - | [[Category: Homo sapiens]]
| + | <div class="pdbe-citations 2i50" style="background-color:#fffaf0;"></div> |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Ubiquitin thiolesterase]]
| + | |
| - | [[Category: Pai, M.T.]]
| + | |
| - | [[Category: ZN]]
| + | |
| - | [[Category: alpha/beta zinc-finger]]
| + | |
| - | [[Category: hydrolase]]
| + | |
| - | [[Category: metalloprotein]]
| + | |
| - | [[Category: ring-finger]]
| + | |
| - | [[Category: ubiquitin]]
| + | |
| - | [[Category: ubiquitin-binding protein]]
| + | |
| - | [[Category: usp]]
| + | |
| - | [[Category: znf-ubp]]
| + | |
| | | | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:16:13 2008''
| + | ==See Also== |
| | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | + | [[Category: Pai M-T]] |
| Structural highlights
Disease
UBP16_HUMAN Note=A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1.
Function
UBP16_HUMAN Specifically deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-10' of histone H3, and is required for chromosome segregation when cells enter into mitosis. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.[1] [2] [3]
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
The BUZ/Znf-UBP domain is a distinct ubiquitin-binding module found in the cytoplasmic deacetylase HDAC6, the E3 ubiquitin ligase BRAP2/IMP, and a subfamily of deubiquitinating enzymes. Here, we report the solution structure of the BUZ domain of Ubp-M, a ubiquitin-specific protease, and its interaction with ubiquitin. Unlike the BUZ domain from isopeptidase T (isoT) that contains a single zinc finger, the Ubp-M BUZ domain features three zinc-binding sites consisting of 12 residues. These zinc ligands form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. In contrast to isoT, which can form an N-terminal loop swapped dimer in the crystal state, the formation of additional zinc fingers in the Ubp-M BUZ domain restricts its N-terminal loop to intra-domain interactions. The ubiquitin-binding site of the Ubp-M BUZ domain is mapped to the highly conserved, concave surface formed by the alpha 3 helix and the central beta-sheet. We further show that this site binds to the C-terminal tail of free ubiquitin, and corresponding peptides display essentially the same binding affinities as full-length ubiquitin does for the Ubp-M BUZ domain. However, modification of the G76(Ub) carboxylate group either by a peptide or isopeptide bond abolishes BUZ-domain interaction. The unique ubiquitin-recognition mode of the BUZ domain family suggests that they may function as "sensors" of free ubiquitin in cells to achieve regulatory roles in many aspects of ubiquitin-dependent processes.
Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin.,Pai MT, Tzeng SR, Kovacs JJ, Keaton MA, Li SS, Yao TP, Zhou P J Mol Biol. 2007 Jul 6;370(2):290-302. Epub 2007 Apr 12. PMID:17512543[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cai SY, Babbitt RW, Marchesi VT. A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and blocks cell division. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2828-33. PMID:10077596
- ↑ Mimnaugh EG, Kayastha G, McGovern NB, Hwang SG, Marcu MG, Trepel J, Cai SY, Marchesi VT, Neckers L. Caspase-dependent deubiquitination of monoubiquitinated nucleosomal histone H2A induced by diverse apoptogenic stimuli. Cell Death Differ. 2001 Dec;8(12):1182-96. PMID:11753566 doi:10.1038/sj.cdd.4400924
- ↑ Joo HY, Zhai L, Yang C, Nie S, Erdjument-Bromage H, Tempst P, Chang C, Wang H. Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature. 2007 Oct 25;449(7165):1068-72. Epub 2007 Oct 3. PMID:17914355 doi:10.1038/nature06256
- ↑ Pai MT, Tzeng SR, Kovacs JJ, Keaton MA, Li SS, Yao TP, Zhou P. Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin. J Mol Biol. 2007 Jul 6;370(2):290-302. Epub 2007 Apr 12. PMID:17512543 doi:10.1016/j.jmb.2007.04.015
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