View source for 1uel


==Solution structure of ubiquitin-like domain of hHR23B complexed with ubiquitin-interacting motif of proteasome subunit S5a==
<StructureSection load='1uel' size='340' side='right'caption='[[1uel]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1uel]] is a 2 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=1UEL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UEL 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uel FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uel OCA], [https://pdbe.org/1uel PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uel RCSB], [https://www.ebi.ac.uk/pdbsum/1uel PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uel ProSAT], [https://www.topsan.org/Proteins/RSGI/1uel TOPSAN]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RD23B_HUMAN RD23B_HUMAN] Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome.<ref>PMID:9372924</ref> <ref>PMID:9734359</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:12815074</ref> <ref>PMID:19435460</ref> <ref>PMID:19941824</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> <ref>PMID:15885096</ref>   Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with CETN2 appears to stabilize XPC. May protect XPC from proteasomal degradation.<ref>PMID:9372924</ref> <ref>PMID:9734359</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:12815074</ref> <ref>PMID:19435460</ref> <ref>PMID:19941824</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> <ref>PMID:15885096</ref>   The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.<ref>PMID:9372924</ref> <ref>PMID:9734359</ref> <ref>PMID:10873465</ref> <ref>PMID:12509299</ref> <ref>PMID:12547395</ref> <ref>PMID:12815074</ref> <ref>PMID:19435460</ref> <ref>PMID:19941824</ref> <ref>PMID:20028083</ref> <ref>PMID:20798892</ref> <ref>PMID:15885096</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/ue/1uel_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=1uel ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves signaling functions that control several cellular processes. The ubiquitination signal is recognized by downstream effectors, many of which carry a ubiquitin-interacting motif (UIM). Such interactions can be modulated by regulators carrying a ubiquitin-like (UbL) domain, which binds UIM by mimicking ubiquitination. Of them, HR23B regulates the proteasomal targeting of ubiquitinated substrates, DNA repair factors, and other proteins. Here we report the structure of the UIM of the proteasome subunit S5a bound to the UbL domain of HR23B. The UbL domain presents one hydrophobic and two polar contact sites for interaction with UIM. The residues in these contact sites are well conserved in ubiquitin, but ubiquitin also presents a histidine at the interface. The pH-dependent protonation of this residue interferes with the access of ubiquitin to the UIM and the ubiquitin-associated domain (UBA), and its mutation to a smaller residue increases the affinity of ubiquitin for UIM.

Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B.,Fujiwara K, Tenno T, Sugasawa K, Jee JG, Ohki I, Kojima C, Tochio H, Hiroaki H, Hanaoka F, Shirakawa M J Biol Chem. 2004 Feb 6;279(6):4760-7. Epub 2003 Oct 29. PMID:14585839<ref>PMID:14585839</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1uel" style="background-color:#fffaf0;"></div>

==See Also==
*[[Proteasome 3D structures|Proteasome 3D structures]]
*[[UV excision repair protein|UV excision repair protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fujiwara K]]
[[Category: Hanaoka H]]
[[Category: Hiroaki H]]
[[Category: Jee JG]]
[[Category: Kojima C]]
[[Category: Ohki I]]
[[Category: Shirakawa M]]
[[Category: Sugasawa K]]
[[Category: Tenno T]]
[[Category: Tochio H]]