6nsv: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6nsv is ON HOLD  until Paper Publication
+==Crystal structure of the human CHIP TPR domain in complex with a 5mer acetylated optimized peptide==
+<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>
+</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>
+<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='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'>[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.
+== 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>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors: Basu, K., Ravalin, M., Bohn, M.-F., Craik, C.S., Gestwicki, J.E.
+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<ref>PMID:31320752</ref>
-Description: Crystal structure of the human CHIP TPR domain in complex with a 5mer acetylated optimized peptide
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6nsv" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: RING-type E3 ubiquitin transferase]]
 [[Category: Basu, K]]
-[[Category: Bohn, M.-F]]
+[[Category: Bohn, M F]]
-[[Category: Gestwicki, J.E]]
+[[Category: Craik, C S]]
+[[Category: Gestwicki, J E]]
 [[Category: Ravalin, M]]
-[[Category: Craik, C.S]]
+[[Category: Chip]]
+[[Category: Ligase]]