1yzb

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[[Image:1yzb.png|left|200px]]
 
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==Solution structure of the Josephin domain of Ataxin-3==
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The line below this paragraph, containing "STRUCTURE_1yzb", creates the "Structure Box" on the page.
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<StructureSection load='1yzb' size='340' side='right'caption='[[1yzb]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1yzb]] 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=1YZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YZB FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1yzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yzb OCA], [https://pdbe.org/1yzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yzb RCSB], [https://www.ebi.ac.uk/pdbsum/1yzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yzb ProSAT]</span></td></tr>
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{{STRUCTURE_1yzb| PDB=1yzb | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[https://omim.org/entry/109150 109150]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN] Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.<ref>PMID:12297501</ref> <ref>PMID:17696782</ref> <ref>PMID:16118278</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yz/1yzb_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1yzb ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The Josephin domain plays an important role in the cellular functions of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. We have determined the solution structure of Josephin and shown that it belongs to the family of papain-like cysteine proteases, sharing the highest degree of structural similarity with bacterial staphopain. A currently unique structural feature of Josephin is a flexible helical hairpin formed by a 32-residue insertion, which could determine substrate specificity. By using the Josephin structure and the availability of NMR chemical shift assignments, we have mapped the enzyme active site by using the typical cysteine protease inhibitors, transepoxysuccinyl-L-eucylamido-4-guanidino-butane (E-64) and [L-3-trans-(propylcarbamyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline (CA-074). We also demonstrate that the specific interaction of Josephin with the ubiquitin-like domain of the ubiquitin- and proteasome-binding factor HHR23B involves complementary exposed hydrophobic surfaces. The structural similarity with other deubiquitinating enzymes suggests a model for the proteolytic enzymatic activity of ataxin-3.
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===Solution structure of the Josephin domain of Ataxin-3===
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The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition.,Nicastro G, Menon RP, Masino L, Knowles PP, McDonald NQ, Pastore A Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10493-8. Epub 2005 Jul 14. PMID:16020535<ref>PMID:16020535</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_16020535}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 1yzb" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16020535 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16020535}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[1yzb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YZB OCA].
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==Reference==
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<ref group="xtra">PMID:16020535</ref><ref group="xtra">PMID:15630566</ref><ref group="xtra">PMID:15544810</ref><ref group="xtra">PMID:12914917</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Knowles, P P.]]
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[[Category: Large Structures]]
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[[Category: Masino, L.]]
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[[Category: Knowles PP]]
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[[Category: McDonald, N Q.]]
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[[Category: Masino L]]
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[[Category: Menon, R P.]]
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[[Category: McDonald NQ]]
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[[Category: Nicastro, G.]]
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[[Category: Menon RP]]
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[[Category: Pastore, A.]]
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[[Category: Nicastro G]]
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[[Category: Papain-like fold]]
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[[Category: Pastore A]]
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[[Category: Transcription]]
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Current revision

Solution structure of the Josephin domain of Ataxin-3

PDB ID 1yzb

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