3a1q
From Proteopedia
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- | [[Image:3a1q.png|left|200px]] | ||
- | + | ==Crystal structure of the mouse RAP80 UIMs in complex with Lys63-linked di-ubiquitin== | |
- | + | <StructureSection load='3a1q' size='340' side='right'caption='[[3a1q]], [[Resolution|resolution]] 2.20Å' scene=''> | |
- | + | == Structural highlights == | |
- | + | <table><tr><td colspan='2'>[[3a1q]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A1Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A1Q 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]] 2.2Å</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=3a1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a1q OCA], [https://pdbe.org/3a1q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a1q RCSB], [https://www.ebi.ac.uk/pdbsum/3a1q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a1q ProSAT]</span></td></tr> |
- | + | </table> | |
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/UBC_MOUSE UBC_MOUSE] Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:19754430</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/a1/3a1q_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=3a1q ConSurf]. | ||
+ | <div style="clear:both"></div> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | RAP80 has a key role in the recruitment of the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA-damage foci for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs (UIMs). Here, we report the crystal structure of the RAP80 tandem UIMs (RAP80-UIM1-UIM2) in complex with Lys 63-linked di-ubiquitin at 2.2 A resolution. The two UIMs, UIM1 and UIM2, and the alpha-helical inter-UIM region together form a continuous 60 A-long alpha-helix. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties, respectively. Both UIM1 and UIM2 of RAP80 recognize an Ile 44-centered hydrophobic patch on ubiquitin but neither UIM interacts with the Lys 63-linked isopeptide bond. Our structure suggests that the inter-UIM region forms a 12 A-long alpha-helix that ensures that the UIMs are arranged to enable specific binding of Lys 63-linked di-ubiquitin. This was confirmed by pull-down analyses using RAP80-UIM1-UIM2 mutants of various length inter-UIM regions. Further, we show that the Epsin1 tandem UIM, which has an inter-UIM region similar to that of RAP80-UIM1-UIM2, also selectively binds Lys 63-linked di-ubiquitin. | ||
- | + | Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80.,Sato Y, Yoshikawa A, Mimura H, Yamashita M, Yamagata A, Fukai S EMBO J. 2009 Aug 19;28(16):2461-8. Epub 2009 Jun 18. PMID:19536136<ref>PMID:19536136</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
- | + | <div class="pdbe-citations 3a1q" style="background-color:#fffaf0;"></div> | |
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- | == | + | |
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==See Also== | ==See Also== | ||
- | *[[ | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
- | + | == References == | |
- | == | + | <references/> |
- | < | + | __TOC__ |
+ | </StructureSection> | ||
+ | [[Category: Large Structures]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
- | [[Category: Fukai | + | [[Category: Fukai S]] |
- | [[Category: Mimura | + | [[Category: Mimura H]] |
- | [[Category: Sato | + | [[Category: Sato Y]] |
- | [[Category: Yamagata | + | [[Category: Yamagata A]] |
- | [[Category: Yamashita | + | [[Category: Yamashita M]] |
- | [[Category: Yoshikawa | + | [[Category: Yoshikawa A]] |
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Current revision
Crystal structure of the mouse RAP80 UIMs in complex with Lys63-linked di-ubiquitin
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Categories: Large Structures | Mus musculus | Fukai S | Mimura H | Sato Y | Yamagata A | Yamashita M | Yoshikawa A