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4kbq

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Revision as of 08:49, 3 April 2019

Structure of the CHIP-TPR domain in complex with the Hsc70 Lid-Tail domains

Structural highlights

4kbq is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4kbo, 2c2l, 3lof, 3q49
Gene:	CHIP, PP1131, STUB1 (HUMAN), HSC70, HSP73, HSPA10, HSPA8 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CHIP_HUMAN] Cerebellar ataxia - hypogonadism. The disease is caused by mutations affecting the gene represented in this entry.

Function

[CHIP_HUMAN] E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. Ubiquitinates NOS1 in concert with Hsp70 and Hsp40. Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90. Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation. Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome. Mediates polyubiquitination of CYP3A4. Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] [HSP7C_HUMAN] Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex.^[9]

Publication Abstract from PubMed

The ubiquitin ligase CHIP plays an important role in cytosolic protein quality control by ubiquitinating proteins chaperoned by Hsp70/Hsc70 and Hsp90, thereby targeting such substrate proteins for degradation. We present a 2.91 A resolution structure of the tetratricopeptide repeat (TPR) domain of CHIP in complex with the alpha-helical lid subdomain and unstructured tail of Hsc70. Surprisingly, the CHIP-TPR interacts with determinants within both the Hsc70-lid subdomain and the C-terminal PTIEEVD motif of the tail, exhibiting an atypical mode of interaction between chaperones and TPR domains. We demonstrate that the interaction between CHIP and the Hsc70-lid subdomain is required for proper ubiquitination of Hsp70/Hsc70 or Hsp70/Hsc70-bound substrate proteins. Posttranslational modifications of the Hsc70 lid and tail disrupt key contacts with the CHIP-TPR and may regulate CHIP-mediated ubiquitination. Our study shows how CHIP docks onto Hsp70/Hsc70 and defines a bipartite mode of interaction between TPR domains and their binding partners.

A Bipartite Interaction between Hsp70 and CHIP Regulates Ubiquitination of Chaperoned Client Proteins.,Zhang H, Amick J, Chakravarti R, Santarriaga S, Schlanger S, McGlone C, Dare M, Nix JC, Scaglione KM, Stuehr DJ, Misra S, Page RC Structure. 2015 Feb 10. pii: S0969-2126(15)00006-4. doi:, 10.1016/j.str.2015.01.003. PMID:25684577^[10]

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

References

↑ Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C. Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol. 1999 Jun;19(6):4535-45. PMID:10330192
↑ Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J, Patterson C. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol. 2001 Jan;3(1):93-6. PMID:11146632 doi:http://dx.doi.org/10.1038/35050618
↑ Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Hohfeld J, Patterson C. CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation. J Biol Chem. 2001 Nov 16;276(46):42938-44. Epub 2001 Sep 13. PMID:11557750 doi:http://dx.doi.org/10.1074/jbc.M101968200
↑ Peng HM, Morishima Y, Jenkins GJ, Dunbar AY, Lau M, Patterson C, Pratt WB, Osawa Y. Ubiquitylation of neuronal nitric-oxide synthase by CHIP, a chaperone-dependent E3 ligase. J Biol Chem. 2004 Dec 17;279(51):52970-7. Epub 2004 Oct 4. PMID:15466472 doi:http://dx.doi.org/10.1074/jbc.M406926200
↑ Pabarcus MK, Hoe N, Sadeghi S, Patterson C, Wiertz E, Correia MA. CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases. Arch Biochem Biophys. 2009 Mar 1;483(1):66-74. doi: 10.1016/j.abb.2008.12.001., Epub 2008 Dec 10. PMID:19103148 doi:10.1016/j.abb.2008.12.001
↑ Annamalai B, Liu X, Gopal U, Isaacs JS. Hsp90 is an essential regulator of EphA2 receptor stability and signaling: implications for cancer cell migration and metastasis. Mol Cancer Res. 2009 Jul;7(7):1021-32. doi: 10.1158/1541-7786.MCR-08-0582. Epub, 2009 Jun 30. PMID:19567782 doi:http://dx.doi.org/10.1158/1541-7786.MCR-08-0582
↑ Parsons JL, Tait PS, Finch D, Dianova II, Edelmann MJ, Khoronenkova SV, Kessler BM, Sharma RA, McKenna WG, Dianov GL. Ubiquitin ligase ARF-BP1/Mule modulates base excision repair. EMBO J. 2009 Oct 21;28(20):3207-15. doi: 10.1038/emboj.2009.243. Epub 2009 Aug, 27. PMID:19713937 doi:10.1038/emboj.2009.243
↑ Matsumura Y, Sakai J, Skach WR. Endoplasmic reticulum protein quality control is determined by cooperative interactions between Hsp/c70 protein and the CHIP E3 ligase. J Biol Chem. 2013 Oct 25;288(43):31069-79. doi: 10.1074/jbc.M113.479345. Epub, 2013 Aug 29. PMID:23990462 doi:http://dx.doi.org/10.1074/jbc.M113.479345
↑ Yahata T, de Caestecker MP, Lechleider RJ, Andriole S, Roberts AB, Isselbacher KJ, Shioda T. The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors. J Biol Chem. 2000 Mar 24;275(12):8825-34. PMID:10722728
↑ Zhang H, Amick J, Chakravarti R, Santarriaga S, Schlanger S, McGlone C, Dare M, Nix JC, Scaglione KM, Stuehr DJ, Misra S, Page RC. A Bipartite Interaction between Hsp70 and CHIP Regulates Ubiquitination of Chaperoned Client Proteins. Structure. 2015 Feb 10. pii: S0969-2126(15)00006-4. doi:, 10.1016/j.str.2015.01.003. PMID:25684577 doi:http://dx.doi.org/10.1016/j.str.2015.01.003

1 Structural highlights
2 Disease
3 Function
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/4kbq"

@@ Line 1: / Line 1: @@
 ==Structure of the CHIP-TPR domain in complex with the Hsc70 Lid-Tail domains==
-<StructureSection load='4kbq' size='340' side='right' caption='[[4kbq]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
+<StructureSection load='4kbq' size='340' side='right'caption='[[4kbq]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4kbq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KBQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KBQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4kbq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KBQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KBQ FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kbo|4kbo]], [[2c2l|2c2l]], [[3lof|3lof]], [[3q49|3q49]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIP, PP1131, STUB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HSC70, HSP73, HSPA10, HSPA8 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kbq OCA], [http://pdbe.org/4kbq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kbq RCSB], [http://www.ebi.ac.uk/pdbsum/4kbq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kbq ProSAT]</span></td></tr>
 </table>
@@ Line 27: / Line 28: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Amick, J]]
 [[Category: Misra, S]]

4kbq

From Proteopedia

Revision as of 08:49, 3 April 2019

Structure of the CHIP-TPR domain in complex with the Hsc70 Lid-Tail domains

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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