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1f4i

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Revision as of 09:46, 21 July 2021

SOLUTION STRUCTURE OF THE HHR23A UBA(2) MUTANT P333E, DEFICIENT IN BINDING THE HIV-1 ACCESSORY PROTEIN VPR

Structural highlights

1f4i is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1dv0
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 DNA repair protein HHR23A is a highly conserved protein that functions in nucleotide excision repair. HHR23A contains two ubiquitin associated domains (UBA) that are conserved in a number of proteins with diverse functions involved in ubiquitination, UV excision repair, and signaling pathways via protein kinases. The cellular binding partners of UBA domains remain unclear; however, we previously found that the HHR23A UBA(2) domain interacts specifically with the HIV-1 Vpr protein. Analysis of the low resolution solution structure of HHR23A UBA(2) revealed a hydrophobic loop region of the UBA(2) domain that we predicted was the interface for protein/protein interactions. Here we present results of in vitro binding studies that demonstrate the requirement of this hydrophobic loop region for interaction with human immunodeficiency virus (HIV-1) Vpr. A single point mutation of the Pro at residue 333 to a Glu totally abolishes the binding of HIV-1 Vpr to UBA(2). High resolution NMR structures of the binding deficient UBA(2) mutant P333E as well as of the wild-type UBA(2) domain were determined to compare the effect of this mutation on the structure. Small but significant differences are observed only locally at the site of the mutation. The biochemical and structural analysis confirms the function of the HHR23A UBA(2) GFP-loop as the protein/protein interacting domain.

Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr.,Withers-Ward ES, Mueller TD, Chen IS, Feigon J Biochemistry. 2000 Nov 21;39(46):14103-12. PMID:11087358^[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
↑ Withers-Ward ES, Mueller TD, Chen IS, Feigon J. Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr. Biochemistry. 2000 Nov 21;39(46):14103-12. PMID:11087358

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/1f4i"

@@ Line 3: / Line 3: @@
 <StructureSection load='1f4i' size='340' side='right'caption='[[1f4i]], [[NMR_Ensembles_of_Models | 21 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1f4i]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F4I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1F4I FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1f4i]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F4I FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dv0|1dv0]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1dv0|1dv0]]</div></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f4i OCA], [http://pdbe.org/1f4i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1f4i RCSB], [http://www.ebi.ac.uk/pdbsum/1f4i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1f4i 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=1f4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f4i OCA], [https://pdbe.org/1f4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f4i RCSB], [https://www.ebi.ac.uk/pdbsum/1f4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f4i 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]]

1f4i

From Proteopedia

Revision as of 09:46, 21 July 2021

SOLUTION STRUCTURE OF THE HHR23A UBA(2) MUTANT P333E, DEFICIENT IN BINDING THE HIV-1 ACCESSORY PROTEIN VPR

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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