1p1a
From Proteopedia
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==NMR structure of ubiquitin-like domain of hHR23B== | ==NMR structure of ubiquitin-like domain of hHR23B== | ||
| - | <StructureSection load='1p1a' size='340' side='right'caption='[[1p1a | + | <StructureSection load='1p1a' size='340' side='right'caption='[[1p1a]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1p1a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[1p1a]] 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=1P1A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P1A FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </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=1p1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p1a OCA], [https://pdbe.org/1p1a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p1a RCSB], [https://www.ebi.ac.uk/pdbsum/1p1a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p1a ProSAT]</span></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=1p1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p1a OCA], [https://pdbe.org/1p1a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p1a RCSB], [https://www.ebi.ac.uk/pdbsum/1p1a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p1a ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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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=1p1a ConSurf]. | </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=1p1a ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | hHR23B is the human homologue of the yeast protein RAD23 and is known to participate in DNA repair by stabilizing xeroderma pigmentosum group C protein. However, hHR23B and RAD23 also have many important functions related to general proteolysis. hHR23B consists of N-terminal ubiquitin-like (UbL), ubiquitin association 1 (UBA1), xeroderma pigmentosum group C binding, and UBA2 domains. The UBA domains interact with ubiquitin (Ub) and inhibit the assembly of polyubiquitin. On the other hand, the UbL domain interacts with the poly-Ub binding site 2 (PUbS2) domain of the S5a protein, which can carry polyubiquitinated substrates into the proteasome. We calculated the NMR structure of the UbL domain of hHR23B and determined binding surfaces of UbL and Ub to UBA1, UBA2, of hHR23B and PUbS2 of S5a by using chemical shift perturbation. Interestingly, the surfaces of UbL and Ub that bind to UBA1, UBA2, and PUbS2 are similar, consisting of five beta-strands and their connecting loops. This is the first report that an intramolecular interaction between UbL and UBA domains is possible, and this interaction could be important for the control of proteolysis by hHR23B. The binding specificities of UbL and Ub for PUbS1, PUbS2, and general ubiquitin-interacting motifs, which share the LALA motif, were evaluated. The UBA domains bind to the surface of Ub including Lys-48, which is required for multiubiquitin assembly, possibly explaining the observed inhibition of multiubiquitination by hHR23B. The UBA domains bind to UbL through electrostatic interactions supported by hydrophobic interactions and to Ub mainly through hydrophobic interactions supported by electrostatic interactions. | ||
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| - | Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a.,Ryu KS, Lee KJ, Bae SH, Kim BK, Kim KA, Choi BS J Biol Chem. 2003 Sep 19;278(38):36621-7. Epub 2003 Jun 28. PMID:12832454<ref>PMID:12832454</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1p1a" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[UV excision repair protein|UV excision repair protein]] | + | *[[UV excision repair protein 3D structures|UV excision repair protein 3D structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Bae | + | [[Category: Bae SH]] |
| - | [[Category: Choi | + | [[Category: Choi BS]] |
| - | [[Category: Kim | + | [[Category: Kim BK]] |
| - | [[Category: Kim | + | [[Category: Kim KA]] |
| - | [[Category: Lee | + | [[Category: Lee KJ]] |
| - | [[Category: Ryu | + | [[Category: Ryu KS]] |
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Revision as of 05:52, 17 April 2024
NMR structure of ubiquitin-like domain of hHR23B
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Categories: Homo sapiens | Large Structures | Bae SH | Choi BS | Kim BK | Kim KA | Lee KJ | Ryu KS
