7t4n - Revision history

OCA at 13:06, 1 March 2024

OCA — Fri, 01 Mar 2024 13:06:55 GMT

←Older revision		Revision as of 13:06, 1 March 2024
Line 3:		Line 3:
	<StructureSection load='7t4n' size='340' side='right'caption='[[7t4n]], [[Resolution\|resolution]] 2.35Å' scene=''>		<StructureSection load='7t4n' size='340' side='right'caption='[[7t4n]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7t4n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T4N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7t4n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pediculus_humanus_corporis Pediculus humanus corporis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T4N FirstGlance]. <br>
-	</td></tr><tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"~~><span class~~=~~'plainlinks'~~>[~~https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase~~]~~, with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=~~2.~~7.11.1 2.7.11.1] </span>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 2.35Å</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=7t4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t4n OCA], [https://pdbe.org/7t4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t4n RCSB], [https://www.ebi.ac.uk/pdbsum/7t4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t4n ProSAT]</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=7t4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t4n OCA], [https://pdbe.org/7t4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t4n RCSB], [https://www.ebi.ac.uk/pdbsum/7t4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t4n ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/PINK1_PEDHC PINK1_PEDHC] Acts as a serine/threonine-protein kinase (PubMed:22645651, PubMed:26161729, PubMed:29160309). Exhibits a substrate preference for proline at position P+1 and a general preference at several residues for basic residues such as arginine (By similarity). Also exhibits moderate preferences for a phosphotyrosine at position P-3 and a tryptophan at P-5 (By similarity). Critical to mitochondrial homeostasis it mediates several pathways that maintain mitochondrial health and function (By similarity) Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as park and likely Drp1, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:26161729). Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (By similarity). Appears to be particularly important in maintaining the physiology and function of cells with high energy demands that are undergoing stress or altered metabolic environment, including spermatids, muscle cells and neurons such as the dopaminergic (DA) neurons (By similarity). Mediates the translocation and activation of park at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:26161729). At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains, the Pink1-phosphorylated polyubiquitin then recruits park from the cytosol to the OMM where park is fully activated by phosphorylation at 'Ser-94' by Pink1 (By similarity). When cellular stress results in irreversible mitochondrial damage, functions with park to promote the clearance of dysfunctional and/or depolarized mitochondria by selective autophagy (mitophagy) (By similarity). The Pink1-park pathway also promotes fission and/or inhibits fusion of damaged mitochondria, by phosphorylating and thus promoting the park-dependent degradation of proteins involved in mitochondrial fusion/fission such as Marf, Opa1 and fzo (By similarity). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (By similarity). Also likely to promote mitochondrial fission independently of park and Atg7-mediated mitophagy, via the phosphorylation and activation of Drp1 (By similarity). Regulates motility of damaged mitochondria by phosphorylating Miro which likely promotes its park-dependent degradation by the proteasome; in motor neurons, this inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria being eliminated in the soma (By similarity). The Pink1-park pathway is also involved in mitochondrial regeneration processes such as promoting mitochondrial biogenesis, activating localized mitochondrial repair, promoting selective turnover of mitochondrial proteins and initiating the mitochondrial import of endogenous proteins (By similarity). Involved in mitochondrial biogenesis by promoting the park-dependent ubiquitination of transcriptional repressor Paris which leads to its subsequent proteasomal degradation and allows activation of the transcription factor srl (By similarity). Functions with park to promote localized mitochondrial repair by activating the translation of specific nuclear-encoded mitochondrial RNAs (nc-mtRNAs) on the mitochondrial surface, including several key electron transport chain component nc-mtRNAs (By similarity). During oogenesis, phosphorylates and inactivates larp on the membrane of defective mitochondria, thus impairing local translation and mtDNA replication and consequently, reducing transmission of deleterious mtDNA mutations to the mature oocyte (By similarity). Phosphorylates the mitochondrial acyl-CoA dehydrogenase Mcad, and appears to be important for maintaining fatty acid and amino acid metabolism via a mechanism that is independent of it's role in maintaining production of ATP (By similarity).[UniProtKB:D6WMX4][UniProtKB:Q0KHV6]<ref>PMID:22645651</ref> <ref>PMID:26161729</ref> <ref>PMID:29160309</ref>
-	~~Mutations in the~~ protein kinase ~~PINK1 lead to defects in mitophagy~~ and ~~cause autosomal recessive early onset Parkinson's Disease~~ (~~EOPD~~)(~~1,2~~). ~~PINK1 has many unique features that enable~~ it to ~~phosphorylate ubiquitin~~ and ~~the ubiquitin-like domain of Parkin~~(~~3-9~~). ~~Structural analysis~~ of ~~PINK1~~ from ~~diverse insect species~~(~~10-12~~) ~~with~~ and ~~without ubiquitin provided snapshots~~ of ~~distinct structural states yet did not explain how PINK1 is activated~~. ~~We here elucidate~~ the activation ~~mechanism~~ of ~~PINK1 by crystallography and cryo-EM. A crystal structure of unphosphorylated Pediculus humanus corporis~~ (Ph) ~~PINK1 resolves a previously omitted N-terminal helix revealing how unphosphorylated yet active PINK1 is oriented on~~ mitochondria. ~~We further reveal a 2.35 A cryo-EM structure of a symmetric PhPINK1 dimer trapped during~~ the ~~process~~ of ~~trans~~-~~autophosphorylation~~, ~~and a 3.1 A cryo~~-~~EM structure of~~ phosphorylated ~~PhPINK1 in~~ the ~~process of undergoing a conformational change~~ to ~~become an active ubiquitin kinase~~. ~~Structures~~ and ~~phosphorylation studies further identify a role for regulatory PINK1 oxidation~~. ~~Together~~, ~~our work delineates~~ the ~~complete activation mechanism~~ of ~~PINK1~~, ~~illuminates how PINK1 interacts~~ with the mitochondrial ~~outer membrane~~, and ~~reveals how PINK1 activity may be modulated~~ by mitochondrial ~~reactive oxygen species.~~	+
-		+
-	~~Activation mechanism~~ of ~~PINK1~~.,~~Gan ZY, Callegari S, Cobbold SA~~, ~~Cotton TR, Mlodzianoski MJ, Schubert AF, Geoghegan ND, Rogers KL, Leis A, Dewson G, Glukhova A, Komander D Nature~~. ~~2021 Dec 21. pii: 10~~.~~1038/s41586~~-~~021~~-~~04340~~-2. ~~doi:~~, 10.~~1038/s41586~~-~~021-04340-2~~. ~~PMID~~:~~34933320~~<ref>PMID:~~34933320~~</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.~~<br>	+
-	</~~div~~>	+
-	<~~div class="pdbe-citations 7t4n" style="background-color~~:~~#fffaf0;">~~</~~div~~>	+
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Pediculus humanus corporis]]
-	[[Category: Dewson, G]]	+	[[Category: Dewson G]]
-	[[Category: Gan~~, Z Y~~]]	+	[[Category: Gan ZY]]
-	[[Category: Glukhova, A]]	+	[[Category: Glukhova A]]
-	[[Category: Komander, D]]	+	[[Category: Komander D]]
-	[[Category: Leis, A]]	+	[[Category: Leis A]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Mitophagy]]~~	+
-	~~[[Category: Parkinson's disease]]~~	+
-	~~[[Category: Phospho-ubiquitin]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Pink1]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Ubiquitin~~]]	+

OCA at 08:46, 23 February 2022

OCA — Wed, 23 Feb 2022 08:46:12 GMT

←Older revision		Revision as of 08:46, 23 February 2022
Line 1:		Line 1:

	==Structure of dimeric unphosphorylated Pediculus humanus (Ph) PINK1 D357A mutant==		==Structure of dimeric unphosphorylated Pediculus humanus (Ph) PINK1 D357A mutant==
-	<StructureSection load='7t4n' size='340' side='right'caption='[[7t4n]]' scene=''>	+	<StructureSection load='7t4n' size='340' side='right'caption='[[7t4n]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T4N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7t4n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T4N FirstGlance]. <br>
-	</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=7t4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t4n OCA], [https://pdbe.org/7t4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t4n RCSB], [https://www.ebi.ac.uk/pdbsum/7t4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t4n ProSAT]</span></td></tr>	+	</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=7t4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t4n OCA], [https://pdbe.org/7t4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t4n RCSB], [https://www.ebi.ac.uk/pdbsum/7t4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t4n ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Mutations in the protein kinase PINK1 lead to defects in mitophagy and cause autosomal recessive early onset Parkinson's Disease (EOPD)(1,2). PINK1 has many unique features that enable it to phosphorylate ubiquitin and the ubiquitin-like domain of Parkin(3-9). Structural analysis of PINK1 from diverse insect species(10-12) with and without ubiquitin provided snapshots of distinct structural states yet did not explain how PINK1 is activated. We here elucidate the activation mechanism of PINK1 by crystallography and cryo-EM. A crystal structure of unphosphorylated Pediculus humanus corporis (Ph) PINK1 resolves a previously omitted N-terminal helix revealing how unphosphorylated yet active PINK1 is oriented on mitochondria. We further reveal a 2.35 A cryo-EM structure of a symmetric PhPINK1 dimer trapped during the process of trans-autophosphorylation, and a 3.1 A cryo-EM structure of phosphorylated PhPINK1 in the process of undergoing a conformational change to become an active ubiquitin kinase. Structures and phosphorylation studies further identify a role for regulatory PINK1 oxidation. Together, our work delineates the complete activation mechanism of PINK1, illuminates how PINK1 interacts with the mitochondrial outer membrane, and reveals how PINK1 activity may be modulated by mitochondrial reactive oxygen species.
		+
		+	Activation mechanism of PINK1.,Gan ZY, Callegari S, Cobbold SA, Cotton TR, Mlodzianoski MJ, Schubert AF, Geoghegan ND, Rogers KL, Leis A, Dewson G, Glukhova A, Komander D Nature. 2021 Dec 21. pii: 10.1038/s41586-021-04340-2. doi:, 10.1038/s41586-021-04340-2. PMID:34933320<ref>PMID:34933320</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7t4n" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dewson G]]	+	[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Gan ZY]]	+	[[Category: Dewson, G]]
-	[[Category: Glukhova A]]	+	[[Category: Gan, Z Y]]
-	[[Category: Komander D]]	+	[[Category: Glukhova, A]]
-	[[Category: Leis A]]	+	[[Category: Komander, D]]
		+	[[Category: Leis, A]]
		+	[[Category: Kinase]]
		+	[[Category: Mitophagy]]
		+	[[Category: Parkinson's disease]]
		+	[[Category: Phospho-ubiquitin]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Pink1]]
		+	[[Category: Transferase]]
		+	[[Category: Ubiquitin]]

OCA at 10:00, 12 January 2022

OCA — Wed, 12 Jan 2022 10:00:18 GMT

←Older revision		Revision as of 10:00, 12 January 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7t4n ~~is ON HOLD~~	+	==Structure of dimeric unphosphorylated Pediculus humanus (Ph) PINK1 D357A mutant==
-		+	<StructureSection load='7t4n' size='340' side='right'caption='[[7t4n]]' scene=''>
-	~~Authors~~: ~~Gan~~, Z.Y., ~~Leis, A~~., ~~Dewson, G~~., ~~Glukhova, A~~., ~~Komander, D~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T4N FirstGlance]. <br>
-	~~Description: Structure of dimeric unphosphorylated Pediculus humanus (Ph) PINK1 D357A mutant~~	+	</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=7t4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t4n OCA], [https://pdbe.org/7t4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t4n RCSB], [https://www.ebi.ac.uk/pdbsum/7t4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t4n ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Dewson, G]]	+	__TOC__
-	[[Category: ~~Leis, A~~]]	+	</StructureSection>
-	[[Category: ~~Komander, D~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Glukhova, A~~]]	+	[[Category: Dewson G]]
-	[[Category: ~~Gan, Z.Y~~]]	+	[[Category: Gan ZY]]
		+	[[Category: Glukhova A]]
		+	[[Category: Komander D]]
		+	[[Category: Leis A]]

OCA: Protected "7t4n" [edit=sysop:move=sysop]

OCA — Wed, 15 Dec 2021 15:46:05 GMT

Protected "7t4n" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:46, 15 December 2021

OCA: New page: '''Unreleased structure''' The entry 7t4n is ON HOLD Authors: Gan, Z.Y., Leis, A., Dewson, G., Glukhova, A., Komander, D. Description: Structure of dimeric unphosphorylated Pediculus h...

OCA — Wed, 15 Dec 2021 15:46:04 GMT

New page: '''Unreleased structure''' The entry 7t4n is ON HOLD Authors: Gan, Z.Y., Leis, A., Dewson, G., Glukhova, A., Komander, D. Description: Structure of dimeric unphosphorylated Pediculus h...

New page

'''Unreleased structure'''

The entry 7t4n is ON HOLD

Authors: Gan, Z.Y., Leis, A., Dewson, G., Glukhova, A., Komander, D.

Description: Structure of dimeric unphosphorylated Pediculus humanus (Ph) PINK1 D357A mutant
[[Category: Unreleased Structures]]
[[Category: Dewson, G]]
[[Category: Leis, A]]
[[Category: Komander, D]]
[[Category: Glukhova, A]]
[[Category: Gan, Z.Y]]