1oqy

From Proteopedia

(Difference between revisions)

Current revision

Structure of the DNA repair protein hHR23a

Structural highlights

1oqy is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RD23A_HUMAN Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin chains in a length-dependent manner and with a lower affinity to 'Lys-63'-linked 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.^[1] ^[2] ^[3] ^[4] ^[5] Involved in nucleotide excision repair and is thought to be functional equivalent for RAD23B in global genome nucleotide excision repair (GG-NER) by association with XPC. In vitro, the XPC:RAD23A dimer has NER activity. Can stabilize XPC.^[6] ^[7] ^[8] ^[9] ^[10] Involved in vpr-dependent replication of HIV-1 in non-proliferating cells and primary macrophages. Required for the association of HIV-1 vpr with the host proteasome.^[11] ^[12] ^[13] ^[14] ^[15]

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 Rad23 family of proteins, including the human homologs hHR23a and hHR23b, stimulates nucleotide excision repair and has been shown to provide a novel link between proteasome-mediated protein degradation and DNA repair. In this work, we illustrate how the proteasomal subunit S5a regulates hHR23a protein structure. By using NMR spectroscopy, we have elucidated the structure and dynamic properties of the 40-kDa hHR23a protein and show it to contain four structured domains connected by flexible linker regions. In addition, we reveal that these domains interact in an intramolecular fashion, and by using residual dipolar coupling data in combination with chemical shift perturbation analysis, we present the hHR23a structure. By itself, hHR23a adopts a closed conformation defined by the interaction of an N-terminal ubiquitin-like domain with two ubiquitin-associated domains. Interestingly, binding of the proteasomal subunit S5a disrupts the hHR23a interdomain interactions and thereby causes it to adopt an opened conformation.

DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a.,Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12694-9. Epub 2003 Oct 13. PMID:14557549^[16]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
↑ Wang Q, Goh AM, Howley PM, Walters KJ. Ubiquitin recognition by the DNA repair protein hHR23a. Biochemistry. 2003 Nov 25;42(46):13529-35. PMID:14621999 doi:10.1021/bi035391j
↑ Raasi S, Pickart CM. Rad23 ubiquitin-associated domains (UBA) inhibit 26 S proteasome-catalyzed proteolysis by sequestering lysine 48-linked polyubiquitin chains. J Biol Chem. 2003 Mar 14;278(11):8951-9. PMID:12643283
↑ Raasi S, Orlov I, Fleming KG, Pickart CM. Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains of HHR23A. J Mol Biol. 2004 Aug 27;341(5):1367-79. PMID:15321727 doi:10.1016/j.jmb.2004.06.057
↑ Li G, Elder RT, Dubrovsky L, Liang D, Pushkarsky T, Chiu K, Fan T, Sire J, Bukrinsky M, Zhao RY. HIV-1 replication through hHR23A-mediated interaction of Vpr with 26S proteasome. PLoS One. 2010 Jun 29;5(6):e11371. doi: 10.1371/journal.pone.0011371. PMID:20614012 doi:10.1371/journal.pone.0011371
↑ Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
↑ Wang Q, Goh AM, Howley PM, Walters KJ. Ubiquitin recognition by the DNA repair protein hHR23a. Biochemistry. 2003 Nov 25;42(46):13529-35. PMID:14621999 doi:10.1021/bi035391j
↑ Raasi S, Pickart CM. Rad23 ubiquitin-associated domains (UBA) inhibit 26 S proteasome-catalyzed proteolysis by sequestering lysine 48-linked polyubiquitin chains. J Biol Chem. 2003 Mar 14;278(11):8951-9. PMID:12643283
↑ Raasi S, Orlov I, Fleming KG, Pickart CM. Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains of HHR23A. J Mol Biol. 2004 Aug 27;341(5):1367-79. PMID:15321727 doi:10.1016/j.jmb.2004.06.057
↑ Li G, Elder RT, Dubrovsky L, Liang D, Pushkarsky T, Chiu K, Fan T, Sire J, Bukrinsky M, Zhao RY. HIV-1 replication through hHR23A-mediated interaction of Vpr with 26S proteasome. PLoS One. 2010 Jun 29;5(6):e11371. doi: 10.1371/journal.pone.0011371. PMID:20614012 doi:10.1371/journal.pone.0011371
↑ Sugasawa K, Ng JM, Masutani C, Maekawa T, Uchida A, van der Spek PJ, Eker AP, Rademakers S, Visser C, Aboussekhra A, Wood RD, Hanaoka F, Bootsma D, Hoeijmakers JH. Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity. Mol Cell Biol. 1997 Dec;17(12):6924-31. PMID:9372924
↑ Wang Q, Goh AM, Howley PM, Walters KJ. Ubiquitin recognition by the DNA repair protein hHR23a. Biochemistry. 2003 Nov 25;42(46):13529-35. PMID:14621999 doi:10.1021/bi035391j
↑ Raasi S, Pickart CM. Rad23 ubiquitin-associated domains (UBA) inhibit 26 S proteasome-catalyzed proteolysis by sequestering lysine 48-linked polyubiquitin chains. J Biol Chem. 2003 Mar 14;278(11):8951-9. PMID:12643283
↑ Raasi S, Orlov I, Fleming KG, Pickart CM. Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains of HHR23A. J Mol Biol. 2004 Aug 27;341(5):1367-79. PMID:15321727 doi:10.1016/j.jmb.2004.06.057
↑ Li G, Elder RT, Dubrovsky L, Liang D, Pushkarsky T, Chiu K, Fan T, Sire J, Bukrinsky M, Zhao RY. HIV-1 replication through hHR23A-mediated interaction of Vpr with 26S proteasome. PLoS One. 2010 Jun 29;5(6):e11371. doi: 10.1371/journal.pone.0011371. PMID:20614012 doi:10.1371/journal.pone.0011371
↑ Walters KJ, Lech PJ, Goh AM, Wang Q, Howley PM. DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12694-9. Epub 2003 Oct 13. PMID:14557549 doi:10.1073/pnas.1634989100

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1oqy"

@@ Line 1: / Line 1: @@
 ==Structure of the DNA repair protein hHR23a==
-<StructureSection load='1oqy' size='340' side='right'caption='[[1oqy]], [[NMR_Ensembles_of_Models | 12 NMR models]]' scene=''>
+<StructureSection load='1oqy' size='340' side='right'caption='[[1oqy]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1oqy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OQY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1OQY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1oqy]] 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=1OQY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OQY FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1qze|1qze]]</div></td></tr>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAD23A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1oqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oqy OCA], [https://pdbe.org/1oqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oqy RCSB], [https://www.ebi.ac.uk/pdbsum/1oqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oqy ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1oqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oqy OCA], [http://pdbe.org/1oqy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1oqy RCSB], [http://www.ebi.ac.uk/pdbsum/1oqy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1oqy ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/RD23A_HUMAN RD23A_HUMAN]] Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin chains in a length-dependent manner and with a lower affinity to 'Lys-63'-linked 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.<ref>PMID:9372924</ref> <ref>PMID:14621999</ref> <ref>PMID:12643283</ref> <ref>PMID:15321727</ref> <ref>PMID:20614012</ref>   Involved in nucleotide excision repair and is thought to be functional equivalent for RAD23B in global genome nucleotide excision repair (GG-NER) by association with XPC. In vitro, the XPC:RAD23A dimer has NER activity. Can stabilize XPC.<ref>PMID:9372924</ref> <ref>PMID:14621999</ref> <ref>PMID:12643283</ref> <ref>PMID:15321727</ref> <ref>PMID:20614012</ref>   Involved in vpr-dependent replication of HIV-1 in non-proliferating cells and primary macrophages. Required for the association of HIV-1 vpr with the host proteasome.<ref>PMID:9372924</ref> <ref>PMID:14621999</ref> <ref>PMID:12643283</ref> <ref>PMID:15321727</ref> <ref>PMID:20614012</ref>
+[https://www.uniprot.org/uniprot/RD23A_HUMAN RD23A_HUMAN] Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin chains in a length-dependent manner and with a lower affinity to 'Lys-63'-linked 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.<ref>PMID:9372924</ref> <ref>PMID:14621999</ref> <ref>PMID:12643283</ref> <ref>PMID:15321727</ref> <ref>PMID:20614012</ref>   Involved in nucleotide excision repair and is thought to be functional equivalent for RAD23B in global genome nucleotide excision repair (GG-NER) by association with XPC. In vitro, the XPC:RAD23A dimer has NER activity. Can stabilize XPC.<ref>PMID:9372924</ref> <ref>PMID:14621999</ref> <ref>PMID:12643283</ref> <ref>PMID:15321727</ref> <ref>PMID:20614012</ref>   Involved in vpr-dependent replication of HIV-1 in non-proliferating cells and primary macrophages. Required for the association of HIV-1 vpr with the host proteasome.<ref>PMID:9372924</ref> <ref>PMID:14621999</ref> <ref>PMID:12643283</ref> <ref>PMID:15321727</ref> <ref>PMID:20614012</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 31: / Line 30: @@
 ==See Also==
-*[[UV excision repair protein|UV excision repair protein]]
+*[[UV excision repair protein 3D structures|UV excision repair protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Goh, A M]]
+[[Category: Goh AM]]
-[[Category: Howley, P M]]
+[[Category: Howley PM]]
-[[Category: Lech, P J]]
+[[Category: Lech PJ]]
-[[Category: Walters, K J]]
+[[Category: Walters KJ]]
-[[Category: Wang, Q]]
+[[Category: Wang Q]]
-[[Category: Dna repair]]
-[[Category: Proteasome-mediated degradation]]
-[[Category: Protein-protein interaction]]
-[[Category: Replication]]

1oqy

From Proteopedia

Current revision

Structure of the DNA repair protein hHR23a

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox