6nsv

From Proteopedia

(Difference between revisions)

Revision as of 06:59, 11 October 2023

Crystal structure of the human CHIP TPR domain in complex with a 5mer acetylated optimized peptide

Structural highlights

6nsv is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.305Å
Ligands:	, , ,
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]

Publication Abstract from PubMed

Protein-protein interactions between E3 ubiquitin ligases and protein termini help shape the proteome. These interactions are sensitive to proteolysis, which alters the ensemble of cellular N and C termini. Here we describe a mechanism wherein caspase activity reveals latent C termini that are then recognized by the E3 ubiquitin ligase CHIP. Using expanded knowledge of CHIP's binding specificity, we predicted hundreds of putative interactions arising from caspase activity. Subsequent validation experiments confirmed that CHIP binds the latent C termini at tau(D421) and caspase-6(D179). CHIP binding to tau(D421), but not tau(FL), promoted its ubiquitination, while binding to caspase-6(D179) mediated ubiquitin-independent inhibition. Given that caspase activity generates tau(D421) in Alzheimer's disease (AD), these results suggested a concise model for CHIP regulation of tau homeostasis. Indeed, we find that loss of CHIP expression in AD coincides with the accumulation of tau(D421) and caspase-6(D179). These results illustrate an unanticipated link between caspases and protein homeostasis.

Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases.,Ravalin M, Theofilas P, Basu K, Opoku-Nsiah KA, Assimon VA, Medina-Cleghorn D, Chen YF, Bohn MF, Arkin M, Grinberg LT, Craik CS, Gestwicki JE Nat Chem Biol. 2019 Aug;15(8):786-794. doi: 10.1038/s41589-019-0322-6. Epub 2019 , Jul 18. PMID:31320752^[9]

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
↑ Ravalin M, Theofilas P, Basu K, Opoku-Nsiah KA, Assimon VA, Medina-Cleghorn D, Chen YF, Bohn MF, Arkin M, Grinberg LT, Craik CS, Gestwicki JE. Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases. Nat Chem Biol. 2019 Aug;15(8):786-794. doi: 10.1038/s41589-019-0322-6. Epub 2019 , Jul 18. PMID:31320752 doi:http://dx.doi.org/10.1038/s41589-019-0322-6

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/6nsv"

@@ Line 3: / Line 3: @@
 <StructureSection load='6nsv' size='340' side='right'caption='[[6nsv]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6nsv]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NSV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NSV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6nsv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NSV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NSV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.305&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=6nsv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nsv OCA], [https://pdbe.org/6nsv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nsv RCSB], [https://www.ebi.ac.uk/pdbsum/6nsv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nsv ProSAT]</span></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=6nsv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nsv OCA], [http://pdbe.org/6nsv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nsv RCSB], [http://www.ebi.ac.uk/pdbsum/6nsv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nsv ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/CHIP_HUMAN CHIP_HUMAN]] Cerebellar ataxia - hypogonadism. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/CHIP_HUMAN CHIP_HUMAN] Cerebellar ataxia - hypogonadism. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/CHIP_HUMAN 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.<ref>PMID:10330192</ref> <ref>PMID:11146632</ref> <ref>PMID:11557750</ref> <ref>PMID:15466472</ref> <ref>PMID:19103148</ref> <ref>PMID:19567782</ref> <ref>PMID:19713937</ref> <ref>PMID:23990462</ref>
+[https://www.uniprot.org/uniprot/CHIP_HUMAN 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.<ref>PMID:10330192</ref> <ref>PMID:11146632</ref> <ref>PMID:11557750</ref> <ref>PMID:15466472</ref> <ref>PMID:19103148</ref> <ref>PMID:19567782</ref> <ref>PMID:19713937</ref> <ref>PMID:23990462</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 </div>
 <div class="pdbe-citations 6nsv" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: RING-type E3 ubiquitin transferase]]
+[[Category: Synthetic construct]]
-[[Category: Basu, K]]
+[[Category: Basu K]]
-[[Category: Bohn, M F]]
+[[Category: Bohn M-F]]
-[[Category: Craik, C S]]
+[[Category: Craik CS]]
-[[Category: Gestwicki, J E]]
+[[Category: Gestwicki JE]]
-[[Category: Ravalin, M]]
+[[Category: Ravalin M]]
-[[Category: Chip]]
-[[Category: Ligase]]

6nsv

From Proteopedia

Revision as of 06:59, 11 October 2023

Crystal structure of the human CHIP TPR domain in complex with a 5mer acetylated optimized peptide

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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