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| | <StructureSection load='1xqr' size='340' side='right'caption='[[1xqr]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='1xqr' size='340' side='right'caption='[[1xqr]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xqr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XQR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xqr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XQR FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xqs|1xqs]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=1xqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xqr OCA], [https://pdbe.org/1xqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xqr RCSB], [https://www.ebi.ac.uk/pdbsum/1xqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xqr 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=1xqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xqr OCA], [https://pdbe.org/1xqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xqr RCSB], [https://www.ebi.ac.uk/pdbsum/1xqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xqr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/HPBP1_HUMAN HPBP1_HUMAN]] Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR.<ref>PMID:9830037</ref> <ref>PMID:10786638</ref> <ref>PMID:12651857</ref> <ref>PMID:15215316</ref>
| + | [https://www.uniprot.org/uniprot/HPBP1_HUMAN HPBP1_HUMAN] Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR.<ref>PMID:9830037</ref> <ref>PMID:10786638</ref> <ref>PMID:12651857</ref> <ref>PMID:15215316</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bracher, A]] | + | [[Category: Bracher A]] |
| - | [[Category: Brodsky, J L]] | + | [[Category: Brodsky JL]] |
| - | [[Category: Chang, H C]] | + | [[Category: Chang HC]] |
| - | [[Category: Dragovic, Z]] | + | [[Category: Dragovic Z]] |
| - | [[Category: Guerriero, V]] | + | [[Category: Guerriero V]] |
| - | [[Category: Hartl, F U]] | + | [[Category: Hartl FU]] |
| - | [[Category: Shomura, Y]] | + | [[Category: Shomura Y]] |
| - | [[Category: Tzvetkov, N]] | + | [[Category: Tzvetkov N]] |
| - | [[Category: Young, J C]] | + | [[Category: Young JC]] |
| - | [[Category: Armadillo repeat]]
| + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Superhelical twist]]
| + | |
| Structural highlights
Function
HPBP1_HUMAN Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR.[1] [2] [3] [4]
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
HspBP1 belongs to a family of eukaryotic proteins recently identified as nucleotide exchange factors for Hsp70. We show that the S. cerevisiae ortholog of HspBP1, Fes1p, is required for efficient protein folding in the cytosol at 37 degrees C. The crystal structure of HspBP1, alone and complexed with part of the Hsp70 ATPase domain, reveals a mechanism for its function distinct from that of BAG-1 or GrpE, previously characterized nucleotide exchange factors of Hsp70. HspBP1 has a curved, all alpha-helical fold containing four armadillo-like repeats unlike the other nucleotide exchange factors. The concave face of HspBP1 embraces lobe II of the ATPase domain, and a steric conflict displaces lobe I, reducing the affinity for nucleotide. In contrast, BAG-1 and GrpE trigger a conserved conformational change in lobe II of the ATPase domain. Thus, nucleotide exchange on eukaryotic Hsp70 occurs through two distinct mechanisms.
Regulation of Hsp70 function by HspBP1: structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange.,Shomura Y, Dragovic Z, Chang HC, Tzvetkov N, Young JC, Brodsky JL, Guerriero V, Hartl FU, Bracher A Mol Cell. 2005 Feb 4;17(3):367-79. PMID:15694338[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Raynes DA, Guerriero V Jr. Inhibition of Hsp70 ATPase activity and protein renaturation by a novel Hsp70-binding protein. J Biol Chem. 1998 Dec 4;273(49):32883-8. PMID:9830037
- ↑ Raynes DA, Guerriero V. Isolation and characterization of isoforms of HspBP1, inhibitors of Hsp70. Biochim Biophys Acta. 2000 Jan 31;1490(1-2):203-7. PMID:10786638
- ↑ McLellan CA, Raynes DA, Guerriero V. HspBP1, an Hsp70 cochaperone, has two structural domains and is capable of altering the conformation of the Hsp70 ATPase domain. J Biol Chem. 2003 May 23;278(21):19017-22. Epub 2003 Mar 21. PMID:12651857 doi:http://dx.doi.org/10.1074/jbc.M301109200
- ↑ Alberti S, Bohse K, Arndt V, Schmitz A, Hohfeld J. The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator. Mol Biol Cell. 2004 Sep;15(9):4003-10. Epub 2004 Jun 23. PMID:15215316 doi:http://dx.doi.org/10.1091/mbc.E04-04-0293
- ↑ Shomura Y, Dragovic Z, Chang HC, Tzvetkov N, Young JC, Brodsky JL, Guerriero V, Hartl FU, Bracher A. Regulation of Hsp70 function by HspBP1: structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange. Mol Cell. 2005 Feb 4;17(3):367-79. PMID:15694338 doi:10.1016/j.molcel.2004.12.023
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