6gy5 - Revision history

OCA at 06:30, 21 August 2019

OCA — Wed, 21 Aug 2019 06:30:11 GMT

←Older revision		Revision as of 06:30, 21 August 2019
Line 1:		Line 1:

	==Crystal structure of the kelch domain of human KLHL20 in complex with DAPK1 peptide==		==Crystal structure of the kelch domain of human KLHL20 in complex with DAPK1 peptide==
-	<StructureSection load='6gy5' size='340' side='right' caption='[[6gy5]], [[Resolution\|resolution]] 1.09Å' scene=''>	+	<StructureSection load='6gy5' size='340' side='right'caption='[[6gy5]], [[Resolution\|resolution]] 1.09Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gy5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GY5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GY5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gy5]] is a 2 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=6GY5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GY5 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KLHL20, KLEIP, KLHLX ([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=6gy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gy5 OCA], [http://pdbe.org/6gy5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gy5 RCSB], [http://www.ebi.ac.uk/pdbsum/6gy5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gy5 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=6gy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gy5 OCA], [http://pdbe.org/6gy5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gy5 RCSB], [http://www.ebi.ac.uk/pdbsum/6gy5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gy5 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/KLH20_HUMAN KLH20_HUMAN]] Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis (PubMed:20389280). The BCR(KLHL20) E3 ubiquitin ligase complex also specifically mediates 'Lys-33'-linked ubiquitination (PubMed:24768539). Involved in anterograde Golgi to endosome transport by mediating 'Lys-33'-linked ubiquitination of CORO7, promoting interaction between CORO7 and EPS15, thereby facilitating actin polymerization and post-Golgi trafficking (PubMed:24768539). Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. The BCR(KLHL20) E3 ubiquitin ligase complex acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11 (PubMed:21670212). In case of tumor, the BCR(KLHL20) E3 ubiquitin ligase complex is involved in tumor hypoxia: following hypoxia, the BCR(KLHL20)complex mediates ubiquitination and degradation of PML, potentiating HIF-1 signaling and cancer progression (PubMed:21840486).<ref>PMID:14528312</ref> <ref>PMID:17395875</ref> <ref>PMID:20389280</ref> <ref>PMID:21670212</ref> <ref>PMID:21840486</ref> <ref>PMID:24768539</ref>		[[http://www.uniprot.org/uniprot/KLH20_HUMAN KLH20_HUMAN]] Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis (PubMed:20389280). The BCR(KLHL20) E3 ubiquitin ligase complex also specifically mediates 'Lys-33'-linked ubiquitination (PubMed:24768539). Involved in anterograde Golgi to endosome transport by mediating 'Lys-33'-linked ubiquitination of CORO7, promoting interaction between CORO7 and EPS15, thereby facilitating actin polymerization and post-Golgi trafficking (PubMed:24768539). Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. The BCR(KLHL20) E3 ubiquitin ligase complex acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11 (PubMed:21670212). In case of tumor, the BCR(KLHL20) E3 ubiquitin ligase complex is involved in tumor hypoxia: following hypoxia, the BCR(KLHL20)complex mediates ubiquitination and degradation of PML, potentiating HIF-1 signaling and cancer progression (PubMed:21840486).<ref>PMID:14528312</ref> <ref>PMID:17395875</ref> <ref>PMID:20389280</ref> <ref>PMID:21670212</ref> <ref>PMID:21840486</ref> <ref>PMID:24768539</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BTB-Kelch proteins form the largest subfamily of Cullin-RING E3 ligases, yet their substrate complexes are mapped and structurally characterized only for KEAP1 and KLHL3. KLHL20 is a related CUL3-dependent ubiquitin ligase linked to autophagy, cancer, and Alzheimer's disease that promotes the ubiquitination and degradation of substrates including DAPK1, PML, and ULK1. We identified an "LPDLV"-containing motif in the DAPK1 death domain that determines its recruitment and degradation by KLHL20. A 1.1-A crystal structure of a KLHL20 Kelch domain-DAPK1 peptide complex reveals DAPK1 binding as a loose helical turn that inserts deeply into the central pocket of the Kelch domain to contact all six blades of the beta propeller. Here, KLHL20 forms salt-bridge and hydrophobic interactions including tryptophan and cysteine residues ideally positioned for covalent inhibitor development. The structure highlights the diverse binding modes of beta-propeller domains versus linear grooves and suggests a new target for structure-based drug design.
		+
		+	Structural Basis for Recruitment of DAPK1 to the KLHL20 E3 Ligase.,Chen Z, Picaud S, Filippakopoulos P, D'Angiolella V, Bullock AN Structure. 2019 Jul 3. pii: S0969-2126(19)30204-7. doi:, 10.1016/j.str.2019.06.005. PMID:31279627<ref>PMID:31279627</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6gy5" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]
	[[Category: Bountra, C]]		[[Category: Bountra, C]]

OCA at 21:58, 9 August 2018

OCA — Thu, 09 Aug 2018 21:58:30 GMT

←Older revision		Revision as of 21:58, 9 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6gy5 ~~is ON HOLD~~	+	==Crystal structure of the kelch domain of human KLHL20 in complex with DAPK1 peptide==
-		+	<StructureSection load='6gy5' size='340' side='right' caption='[[6gy5]], [[Resolution\|resolution]] 1.09Å' scene=''>
-	~~Authors~~: ~~Chen, Z~~.~~, Hozjan, V~~.~~, Strain~~-~~Damerell, C~~.~~, Williams, E~~.~~, Wang, D~~.~~, Cooper, C~~.D.O., ~~Sanvitale~~, ~~C.E.~~, ~~Fairhead, M~~.~~, Carpenter, E~~.P., ~~Pike, A~~.C.W., ~~Krojer, T~~., ~~Srikannathasan, V~~.~~, Sorrell, F~~.~~, Johansson, C~~., ~~Mathea, S~~., ~~Burgess~~-~~Brown, N~~.~~, von Delft, F~~.~~, Arrowsmith, C~~.H., ~~Edwards~~, A.M., ~~Bountra~~, C.~~, Bullock, A~~.N.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6gy5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GY5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GY5 FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of the ~~kelch domain of human~~ KLHL20 in complex ~~with DAPK1 peptide~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	<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=6gy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gy5 OCA], [http://pdbe.org/6gy5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gy5 RCSB], [http://www.ebi.ac.uk/pdbsum/6gy5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gy5 ProSAT]</span></td></tr>
-	~~[[Category~~: ~~Mathea, S]]~~	+	</table>
-	[[Category: ~~Sanvitale~~, C.E]]	+	== Function ==
-	[[Category: ~~Pike~~, A.C.W]]	+	[[http://www.uniprot.org/uniprot/KLH20_HUMAN KLH20_HUMAN]] Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis (PubMed:20389280). The BCR(KLHL20) E3 ubiquitin ligase complex also specifically mediates 'Lys-33'-linked ubiquitination (PubMed:24768539). Involved in anterograde Golgi to endosome transport by mediating 'Lys-33'-linked ubiquitination of CORO7, promoting interaction between CORO7 and EPS15, thereby facilitating actin polymerization and post-Golgi trafficking (PubMed:24768539). Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. The BCR(KLHL20) E3 ubiquitin ligase complex acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11 (PubMed:21670212). In case of tumor, the BCR(KLHL20) E3 ubiquitin ligase complex is involved in tumor hypoxia: following hypoxia, the BCR(KLHL20)complex mediates ubiquitination and degradation of PML, potentiating HIF-1 signaling and cancer progression (PubMed:21840486).<ref>PMID:14528312</ref> <ref>PMID:17395875</ref> <ref>PMID:20389280</ref> <ref>PMID:21670212</ref> <ref>PMID:21840486</ref> <ref>PMID:24768539</ref>
-	[[Category: ~~Arrowsmith~~, ~~C.H~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Arrowsmith, C H]]
		+	[[Category: Bountra, C]]
		+	[[Category: Bullock, A N]]
	[[Category: Burgess-Brown, N]]		[[Category: Burgess-Brown, N]]
		+	[[Category: Carpenter, E P]]
		+	[[Category: Chen, Z]]
		+	[[Category: Cooper, C D.O]]
		+	[[Category: Delft, F von]]
		+	[[Category: Edwards, A M]]
		+	[[Category: Fairhead, M]]
	[[Category: Hozjan, V]]		[[Category: Hozjan, V]]
-	[[Category: Williams, E]]
-	[[Category: Fairhead, M]]
-	[[Category: Wang, D]]
-	[[Category: Von Delft, F]]
-	[[Category: Bullock, A.N]]
-	[[Category: Edwards, A.M]]
	[[Category: Johansson, C]]		[[Category: Johansson, C]]
-	[[Category: Chen, Z]]
-	[[Category: Strain-Damerell, C]]
	[[Category: Krojer, T]]		[[Category: Krojer, T]]
-	[[Category: ~~Cooper~~, C.~~D.O~~]]	+	[[Category: Mathea, S]]
		+	[[Category: Pike, A C.W]]
		+	[[Category: Sanvitale, C E]]
		+	[[Category: Sorrell, F]]
	[[Category: Srikannathasan, V]]		[[Category: Srikannathasan, V]]
-	[[Category: ~~Bountra~~, C]]	+	[[Category: Strain-Damerell, C]]
-	[[Category: ~~Sorrell~~, F]]	+	[[Category: Wang, D]]
-	[[Category: ~~Carpenter~~, E.P]]	+	[[Category: Williams, E]]
		+	[[Category: Complex]]
		+	[[Category: Death domain]]
		+	[[Category: E3 ligase]]
		+	[[Category: Kelch domain]]
		+	[[Category: Ligase]]
		+	[[Category: Substrate]]
		+	[[Category: Ubiquitination]]

OCA: Protected "6gy5" [edit=sysop:move=sysop]

OCA — Wed, 04 Jul 2018 05:59:05 GMT

Protected "6gy5" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:59, 4 July 2018

OCA: New page: '''Unreleased structure''' The entry 6gy5 is ON HOLD Authors: Chen, Z., Hozjan, V., Strain-Damerell, C., Williams, E., Wang, D., Cooper, C.D.O., Sanvitale, C.E., Fairhead, M., Carpenter...

OCA — Wed, 04 Jul 2018 05:59:03 GMT

New page: '''Unreleased structure''' The entry 6gy5 is ON HOLD Authors: Chen, Z., Hozjan, V., Strain-Damerell, C., Williams, E., Wang, D., Cooper, C.D.O., Sanvitale, C.E., Fairhead, M., Carpenter...

New page

'''Unreleased structure'''

The entry 6gy5 is ON HOLD

Authors: Chen, Z., Hozjan, V., Strain-Damerell, C., Williams, E., Wang, D., Cooper, C.D.O., Sanvitale, C.E., Fairhead, M., Carpenter, E.P., Pike, A.C.W., Krojer, T., Srikannathasan, V., Sorrell, F., Johansson, C., Mathea, S., Burgess-Brown, N., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Bullock, A.N.

Description: Crystal structure of the kelch domain of human KLHL20 in complex with DAPK1 peptide
[[Category: Unreleased Structures]]
[[Category: Mathea, S]]
[[Category: Sanvitale, C.E]]
[[Category: Pike, A.C.W]]
[[Category: Arrowsmith, C.H]]
[[Category: Burgess-Brown, N]]
[[Category: Hozjan, V]]
[[Category: Williams, E]]
[[Category: Fairhead, M]]
[[Category: Wang, D]]
[[Category: Von Delft, F]]
[[Category: Bullock, A.N]]
[[Category: Edwards, A.M]]
[[Category: Johansson, C]]
[[Category: Chen, Z]]
[[Category: Strain-Damerell, C]]
[[Category: Krojer, T]]
[[Category: Cooper, C.D.O]]
[[Category: Srikannathasan, V]]
[[Category: Bountra, C]]
[[Category: Sorrell, F]]
[[Category: Carpenter, E.P]]