7lht - Revision history

OCA at 14:59, 6 March 2024

OCA — Wed, 06 Mar 2024 14:59:25 GMT

←Older revision		Revision as of 14:59, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='7lht' size='340' side='right'caption='[[7lht]], [[Resolution\|resolution]] 3.50Å' scene=''>		<StructureSection load='7lht' size='340' side='right'caption='[[7lht]], [[Resolution\|resolution]] 3.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7lht]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LHT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lht]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LHT FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>~~, ~~<scene name='pdbligand=GDP:GUANOSINE-~~5~~-DIPHOSPHATE'>GDP</scene>~~</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]] 3.5Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~LRRK2, PARK8 ([https~~:/~~/www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=5~~&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></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=7lht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lht OCA], [https://pdbe.org/7lht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lht RCSB], [https://www.ebi.ac.uk/pdbsum/7lht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lht 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=7lht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lht OCA], [https://pdbe.org/7lht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lht RCSB], [https://www.ebi.ac.uk/pdbsum/7lht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lht ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/LRRK2_HUMAN LRRK2_HUMAN]] Defects in LRRK2 are the cause of Parkinson disease type 8 (PARK8) [MIM:[https://omim.org/entry/607060 607060]]. A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.<ref>PMID:21850687</ref> <ref>PMID:16321986</ref> <ref>PMID:16269541</ref> <ref>PMID:15541309</ref> <ref>PMID:15541308</ref> <ref>PMID:16081470</ref> <ref>PMID:16087219</ref> <ref>PMID:15726496</ref> <ref>PMID:15732108</ref> <ref>PMID:15852371</ref> <ref>PMID:16240353</ref> <ref>PMID:15880653</ref> <ref>PMID:15929036</ref> <ref>PMID:16251215</ref> <ref>PMID:16272164</ref> <ref>PMID:16333314</ref> <ref>PMID:16272257</ref> <ref>PMID:15680455</ref> <ref>PMID:15680456</ref> <ref>PMID:15680457</ref> <ref>PMID:15811454</ref> <ref>PMID:16250030</ref> <ref>PMID:16172858</ref> <ref>PMID:16157901</ref> <ref>PMID:16247070</ref> <ref>PMID:16157908</ref> <ref>PMID:16157909</ref> <ref>PMID:15925109</ref> <ref>PMID:16298482</ref> <ref>PMID:16102999</ref> <ref>PMID:16533964</ref> <ref>PMID:17019612</ref> <ref>PMID:18213618</ref> <ref>PMID:21641266</ref>	+	[https://www.uniprot.org/uniprot/LRRK2_HUMAN LRRK2_HUMAN] Defects in LRRK2 are the cause of Parkinson disease type 8 (PARK8) [MIM:[https://omim.org/entry/607060 607060]. A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.<ref>PMID:21850687</ref> <ref>PMID:16321986</ref> <ref>PMID:16269541</ref> <ref>PMID:15541309</ref> <ref>PMID:15541308</ref> <ref>PMID:16081470</ref> <ref>PMID:16087219</ref> <ref>PMID:15726496</ref> <ref>PMID:15732108</ref> <ref>PMID:15852371</ref> <ref>PMID:16240353</ref> <ref>PMID:15880653</ref> <ref>PMID:15929036</ref> <ref>PMID:16251215</ref> <ref>PMID:16272164</ref> <ref>PMID:16333314</ref> <ref>PMID:16272257</ref> <ref>PMID:15680455</ref> <ref>PMID:15680456</ref> <ref>PMID:15680457</ref> <ref>PMID:15811454</ref> <ref>PMID:16250030</ref> <ref>PMID:16172858</ref> <ref>PMID:16157901</ref> <ref>PMID:16247070</ref> <ref>PMID:16157908</ref> <ref>PMID:16157909</ref> <ref>PMID:15925109</ref> <ref>PMID:16298482</ref> <ref>PMID:16102999</ref> <ref>PMID:16533964</ref> <ref>PMID:17019612</ref> <ref>PMID:18213618</ref> <ref>PMID:21641266</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/LRRK2_HUMAN LRRK2_HUMAN]] May play a role in the phosphorylation of proteins central to Parkinson disease. Phosphorylates PRDX3. May also have GTPase activity. Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes.<ref>PMID:16352719</ref> <ref>PMID:20949042</ref> <ref>PMID:21850687</ref> <ref>PMID:22012985</ref>	+	[https://www.uniprot.org/uniprot/LRRK2_HUMAN LRRK2_HUMAN] May play a role in the phosphorylation of proteins central to Parkinson disease. Phosphorylates PRDX3. May also have GTPase activity. Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes.<ref>PMID:16352719</ref> <ref>PMID:20949042</ref> <ref>PMID:21850687</ref> <ref>PMID:22012985</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Mutations in leucine-rich repeat kinase 2 (LRRK2) are commonly implicated in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 regulates critical cellular processes at membranous organelles and forms microtubule-based pathogenic filaments, yet the molecular basis underlying these biological roles of LRRK2 remains largely enigmatic. Here, we determined high-resolution structures of full-length human LRRK2, revealing its architecture and key interdomain scaffolding elements for rationalizing disease-causing mutations. The kinase domain of LRRK2 is captured in an inactive state, a conformation also adopted by the most common PD-associated mutation, LRRK2(G2019S). This conformation serves as a framework for structure-guided design of conformational specific inhibitors. We further determined the structure of COR-mediated LRRK2 dimers and found that single-point mutations at the dimer interface abolished pathogenic filamentation in cells. Overall, our study provides mechanistic insights into physiological and pathological roles of LRRK2 and establishes a structural template for future therapeutic intervention in PD.	+

-	~~Structural analysis of the full-length human~~ LRRK2~~.,Myasnikov A, Zhu H, Hixson P, Xie B, Yu K, Pitre A, Peng J, Sun J Cell. 2021 Jun 3. pii: S0092-8674(21)00601-2. doi: 10.1016/j.cell.2021.05.004. PMID:34107286<ref>PMID:34107286</ref>~~	+	==See Also==
-		+	*[[LRRK2 3D structures\|LRRK2 3D structures]]
-	~~From MEDLINE®~~/~~PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
-	~~</div>~~	+
-	~~<div class="pdbe-citations 7lht" style="background-color:#fffaf0;"><~~/~~div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hixson, P]]	+	[[Category: Hixson P]]
-	[[Category: Myasnikov, A]]	+	[[Category: Myasnikov A]]
-	[[Category: Peng, J]]	+	[[Category: Peng J]]
-	[[Category: Pitre, A]]	+	[[Category: Pitre A]]
-	[[Category: Sun, J]]	+	[[Category: Sun J]]
-	[[Category: Xie, B]]	+	[[Category: Xie B]]
-	[[Category: Yu, K]]	+	[[Category: Yu K]]
-	[[Category: Zhu, H]]	+	[[Category: Zhu H]]
-	~~[[Category: Cryo-em]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Microtubule]]~~	+
-	~~[[Category: Neuropeptide]]~~	+
-	~~[[Category: Parkinson's disease]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 10:10, 14 July 2021

OCA — Wed, 14 Jul 2021 10:10:36 GMT

←Older revision		Revision as of 10:10, 14 July 2021
Line 1:		Line 1:

	==Structure of the LRRK2 dimer==		==Structure of the LRRK2 dimer==
-	<StructureSection load='7lht' size='340' side='right'caption='[[7lht]]' scene=''>	+	<StructureSection load='7lht' size='340' side='right'caption='[[7lht]], [[Resolution\|resolution]] 3.50Å' 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=7LHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LHT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lht]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LHT 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=7lht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lht OCA], [https://pdbe.org/7lht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lht RCSB], [https://www.ebi.ac.uk/pdbsum/7lht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lht ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LRRK2, PARK8 ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7lht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lht OCA], [https://pdbe.org/7lht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lht RCSB], [https://www.ebi.ac.uk/pdbsum/7lht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lht ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[https://www.uniprot.org/uniprot/LRRK2_HUMAN LRRK2_HUMAN]] Defects in LRRK2 are the cause of Parkinson disease type 8 (PARK8) [MIM:[https://omim.org/entry/607060 607060]]. A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.<ref>PMID:21850687</ref> <ref>PMID:16321986</ref> <ref>PMID:16269541</ref> <ref>PMID:15541309</ref> <ref>PMID:15541308</ref> <ref>PMID:16081470</ref> <ref>PMID:16087219</ref> <ref>PMID:15726496</ref> <ref>PMID:15732108</ref> <ref>PMID:15852371</ref> <ref>PMID:16240353</ref> <ref>PMID:15880653</ref> <ref>PMID:15929036</ref> <ref>PMID:16251215</ref> <ref>PMID:16272164</ref> <ref>PMID:16333314</ref> <ref>PMID:16272257</ref> <ref>PMID:15680455</ref> <ref>PMID:15680456</ref> <ref>PMID:15680457</ref> <ref>PMID:15811454</ref> <ref>PMID:16250030</ref> <ref>PMID:16172858</ref> <ref>PMID:16157901</ref> <ref>PMID:16247070</ref> <ref>PMID:16157908</ref> <ref>PMID:16157909</ref> <ref>PMID:15925109</ref> <ref>PMID:16298482</ref> <ref>PMID:16102999</ref> <ref>PMID:16533964</ref> <ref>PMID:17019612</ref> <ref>PMID:18213618</ref> <ref>PMID:21641266</ref>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/LRRK2_HUMAN LRRK2_HUMAN]] May play a role in the phosphorylation of proteins central to Parkinson disease. Phosphorylates PRDX3. May also have GTPase activity. Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes.<ref>PMID:16352719</ref> <ref>PMID:20949042</ref> <ref>PMID:21850687</ref> <ref>PMID:22012985</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Mutations in leucine-rich repeat kinase 2 (LRRK2) are commonly implicated in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 regulates critical cellular processes at membranous organelles and forms microtubule-based pathogenic filaments, yet the molecular basis underlying these biological roles of LRRK2 remains largely enigmatic. Here, we determined high-resolution structures of full-length human LRRK2, revealing its architecture and key interdomain scaffolding elements for rationalizing disease-causing mutations. The kinase domain of LRRK2 is captured in an inactive state, a conformation also adopted by the most common PD-associated mutation, LRRK2(G2019S). This conformation serves as a framework for structure-guided design of conformational specific inhibitors. We further determined the structure of COR-mediated LRRK2 dimers and found that single-point mutations at the dimer interface abolished pathogenic filamentation in cells. Overall, our study provides mechanistic insights into physiological and pathological roles of LRRK2 and establishes a structural template for future therapeutic intervention in PD.
		+
		+	Structural analysis of the full-length human LRRK2.,Myasnikov A, Zhu H, Hixson P, Xie B, Yu K, Pitre A, Peng J, Sun J Cell. 2021 Jun 3. pii: S0092-8674(21)00601-2. doi: 10.1016/j.cell.2021.05.004. PMID:34107286<ref>PMID:34107286</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lht" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hixson P]]	+	[[Category: Hixson, P]]
-	[[Category: Myasnikov A]]	+	[[Category: Myasnikov, A]]
-	[[Category: Peng J]]	+	[[Category: Peng, J]]
-	[[Category: Pitre A]]	+	[[Category: Pitre, A]]
-	[[Category: Sun J]]	+	[[Category: Sun, J]]
-	[[Category: Xie B]]	+	[[Category: Xie, B]]
-	[[Category: Yu K]]	+	[[Category: Yu, K]]
-	[[Category: Zhu H]]	+	[[Category: Zhu, H]]
		+	[[Category: Cryo-em]]
		+	[[Category: Hydrolase]]
		+	[[Category: Kinase]]
		+	[[Category: Microtubule]]
		+	[[Category: Neuropeptide]]
		+	[[Category: Parkinson's disease]]
		+	[[Category: Transferase]]

OCA at 14:46, 17 June 2021

OCA — Thu, 17 Jun 2021 14:46:54 GMT

←Older revision		Revision as of 14:46, 17 June 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7lht is ~~ON HOLD until Paper Publication~~	+	==Structure of the LRRK2 dimer==
-		+	<StructureSection load='7lht' size='340' side='right'caption='[[7lht]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LHT FirstGlance]. <br>
-	~~Description~~:	+	</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=7lht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lht OCA], [https://pdbe.org/7lht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lht RCSB], [https://www.ebi.ac.uk/pdbsum/7lht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lht ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Hixson P]]
		+	[[Category: Myasnikov A]]
		+	[[Category: Peng J]]
		+	[[Category: Pitre A]]
		+	[[Category: Sun J]]
		+	[[Category: Xie B]]
		+	[[Category: Yu K]]
		+	[[Category: Zhu H]]

OCA at 07:53, 26 May 2021

OCA — Wed, 26 May 2021 07:53:29 GMT

←Older revision		Revision as of 07:53, 26 May 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7lht is ON HOLD	+	The entry 7lht is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 03 Feb 2021 09:29:42 GMT

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

←Older revision

Revision as of 09:29, 3 February 2021

OCA: New page: '''Unreleased structure''' The entry 7lht is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 03 Feb 2021 09:29:40 GMT

New page: '''Unreleased structure''' The entry 7lht is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7lht is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]