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4wv7

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HEAT SHOCK PROTEIN 70 SUBSTRATE BINDING DOMAIN WITH COVALENTLY LINKED NOVOLACTONE

Structural highlights

4wv7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.42Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HS71A_HUMAN In cooperation with other chaperones, Hsp70s stabilize preexistent proteins against aggregation and mediate the folding of newly translated polypeptides in the cytosol as well as within organelles. These chaperones participate in all these processes through their ability to recognize nonnative conformations of other proteins. They bind extended peptide segments with a net hydrophobic character exposed by polypeptides during translation and membrane translocation, or following stress-induced damage. In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223).^[1] ^[2] ^[3]

Publication Abstract from PubMed

The highly conserved 70 kDa heat shock proteins (Hsp70) play an integral role in proteostasis such that dysregulation has been implicated in numerous diseases. Elucidating the precise role of Hsp70 family members in the cellular context, however, has been hampered by the redundancy and intricate regulation of the chaperone network, and relatively few selective and potent tools. We have characterized a natural product, novolactone, that targets cytosolic and ER-localized isoforms of Hsp70 through a highly conserved covalent interaction at the interface between the substrate-binding and ATPase domains. Biochemical and structural analyses indicate that novolactone disrupts interdomain communication by allosterically inducing a conformational change in the Hsp70 protein to block ATP-induced substrate release and inhibit refolding activities. Thus, novolactone is a valuable tool for exploring the requirements of Hsp70 chaperones in diverse cellular contexts.

The Novolactone Natural Product Disrupts the Allosteric Regulation of Hsp70.,Hassan AQ, Kirby CA, Zhou W, Schuhmann T, Kityk R, Kipp DR, Baird J, Chen J, Chen Y, Chung F, Hoepfner D, Movva NR, Pagliarini R, Petersen F, Quinn C, Quinn D, Riedl R, Schmitt EK, Schitter A, Stams T, Studer C, Fortin PD, Mayer MP, Sadlish H Chem Biol. 2014 Dec 23. pii: S1074-5521(14)00415-3. doi:, 10.1016/j.chembiol.2014.11.007. PMID:25544045^[4]

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

References

↑ Perez-Vargas J, Romero P, Lopez S, Arias CF. The peptide-binding and ATPase domains of recombinant hsc70 are required to interact with rotavirus and reduce its infectivity. J Virol. 2006 Apr;80(7):3322-31. PMID:16537599 doi:http://dx.doi.org/80/7/3322
↑ Liu X, Liu D, Qian D, Dai J, An Y, Jiang S, Stanley B, Yang J, Wang B, Liu X, Liu DX. Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5 (ATF5) protein and promotes proteasome- and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells. J Biol Chem. 2012 Jun 1;287(23):19599-609. doi: 10.1074/jbc.M112.363622. Epub, 2012 Apr 23. PMID:22528486 doi:http://dx.doi.org/10.1074/jbc.M112.363622
↑ Chen Z, Barbi J, Bu S, Yang HY, Li Z, Gao Y, Jinasena D, Fu J, Lin F, Chen C, Zhang J, Yu N, Li X, Shan Z, Nie J, Gao Z, Tian H, Li Y, Yao Z, Zheng Y, Park BV, Pan Z, Zhang J, Dang E, Li Z, Wang H, Luo W, Li L, Semenza GL, Zheng SG, Loser K, Tsun A, Greene MI, Pardoll DM, Pan F, Li B. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3. Immunity. 2013 Aug 22;39(2):272-85. doi: 10.1016/j.immuni.2013.08.006. PMID:23973223 doi:http://dx.doi.org/10.1016/j.immuni.2013.08.006
↑ Hassan AQ, Kirby CA, Zhou W, Schuhmann T, Kityk R, Kipp DR, Baird J, Chen J, Chen Y, Chung F, Hoepfner D, Movva NR, Pagliarini R, Petersen F, Quinn C, Quinn D, Riedl R, Schmitt EK, Schitter A, Stams T, Studer C, Fortin PD, Mayer MP, Sadlish H. The Novolactone Natural Product Disrupts the Allosteric Regulation of Hsp70. Chem Biol. 2014 Dec 23. pii: S1074-5521(14)00415-3. doi:, 10.1016/j.chembiol.2014.11.007. PMID:25544045 doi:http://dx.doi.org/10.1016/j.chembiol.2014.11.007

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4wv7"

Categories: Homo sapiens | Large Structures | Baird J | Kirby CA | Stams T

@@ Line 1: / Line 1: @@
 ==HEAT SHOCK PROTEIN 70 SUBSTRATE BINDING DOMAIN WITH COVALENTLY LINKED NOVOLACTONE==
-<StructureSection load='4wv7' size='340' side='right' caption='[[4wv7]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
+<StructureSection load='4wv7' size='340' side='right'caption='[[4wv7]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4wv7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WV7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4wv7]] 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=4WV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WV7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3UM:(5BETA,6ALPHA,8ALPHA,14ALPHA)-13-ETHENYL-5,6-DIHYDROXY-14-METHYLPODOCARP-12-EN-15-OIC+ACID'>3UM</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]] 2.42&#8491;</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=4wv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wv7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wv7 RCSB], [http://www.ebi.ac.uk/pdbsum/4wv7 PDBsum]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3UM:(5BETA,6ALPHA,8ALPHA,14ALPHA)-13-ETHENYL-5,6-DIHYDROXY-14-METHYLPODOCARP-12-EN-15-OIC+ACID'>3UM</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=4wv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wv7 OCA], [https://pdbe.org/4wv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wv7 RCSB], [https://www.ebi.ac.uk/pdbsum/4wv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wv7 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/HS71A_HUMAN HS71A_HUMAN] In cooperation with other chaperones, Hsp70s stabilize preexistent proteins against aggregation and mediate the folding of newly translated polypeptides in the cytosol as well as within organelles. These chaperones participate in all these processes through their ability to recognize nonnative conformations of other proteins. They bind extended peptide segments with a net hydrophobic character exposed by polypeptides during translation and membrane translocation, or following stress-induced damage. In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223).<ref>PMID:16537599</ref> <ref>PMID:22528486</ref> <ref>PMID:23973223</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 14: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4wv7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Heat Shock Protein structures|Heat Shock Protein structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Baird, J]]
+[[Category: Homo sapiens]]
-[[Category: Kirby, C A]]
+[[Category: Large Structures]]
-[[Category: Stams, T]]
+[[Category: Baird J]]
-[[Category: Allosteric inhibitor]]
+[[Category: Kirby CA]]
-[[Category: Chaperone-chaperone inhibitor complex]]
+[[Category: Stams T]]

4wv7

From Proteopedia

Current revision

HEAT SHOCK PROTEIN 70 SUBSTRATE BINDING DOMAIN WITH COVALENTLY LINKED NOVOLACTONE

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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