OCA at 11:01, 3 January 2024

2024-01-03T11:01:12Z

←Older revision		Revision as of 11:01, 3 January 2024
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-	'''Unreleased structure'''

-	~~The entry~~ 8fo2 is ~~ON HOLD~~	+	==Cryo-EM structure of Rab29-LRRK2 complex in the LRRK2 monomer state==
		+	<StructureSection load='8fo2' size='340' side='right'caption='[[8fo2]], [[Resolution\|resolution]] 4.13Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8fo2]] 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=8FO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FO2 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 4.13Å</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>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8fo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fo2 OCA], [https://pdbe.org/8fo2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fo2 RCSB], [https://www.ebi.ac.uk/pdbsum/8fo2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fo2 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/RAB7L_HUMAN RAB7L_HUMAN] The small GTPases Rab are key regulators in vesicle trafficking (PubMed:24788816). Essential for maintaining the integrity of the endosome-trans-Golgi network structure (By similarity). Together with LRRK2, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:24788816). Recruits LRRK2 to the Golgi complex and stimulates LRRK2 kinase activity (PubMed:29212815). Regulates neuronal process morphology in the intact central nervous system (CNS) (By similarity). May play a role in the formation of typhoid toxin transport intermediates during Salmonella enterica serovar Typhi (S.Typhi) epithelial cell infection (PubMed:22042847).[UniProtKB:Q63481]<ref>PMID:22042847</ref> <ref>PMID:24788816</ref> <ref>PMID:29212815</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Gain-of-function mutations in LRRK2, which encodes the leucine-rich repeat kinase 2 (LRRK2), are the most common genetic cause of late-onset Parkinson's disease. LRRK2 is recruited to membrane organelles and activated by Rab29, a Rab guanosine triphosphatase encoded in the PARK16 locus. We present cryo-electron microscopy structures of Rab29-LRRK2 complexes in three oligomeric states, providing key snapshots during LRRK2 recruitment and activation. Rab29 induces an unexpected tetrameric assembly of LRRK2, formed by two kinase-active central protomers and two kinase-inactive peripheral protomers. The central protomers resemble the active-like state trapped by the type I kinase inhibitor DNL201, a compound that underwent a phase 1 clinical trial. Our work reveals the structural mechanism of LRRK2 spatial regulation and provides insights into LRRK2 inhibitor design for Parkinson's disease treatment.

-	~~Authors~~:	+	Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2.,Zhu H, Tonelli F, Turk M, Prescott A, Alessi DR, Sun J Science. 2023 Dec 22;382(6677):1404-1411. doi: 10.1126/science.adi9926. Epub 2023 , Dec 21. PMID:38127736<ref>PMID:38127736</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8fo2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Sun J]]
		+	[[Category: Zhu H]]

OCA: Protected "8fo2" [edit=sysop:move=sysop]

2023-01-11T05:57:00Z

Protected "8fo2" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:57, 11 January 2023

OCA: New page: '''Unreleased structure''' The entry 8fo2 is ON HOLD Authors: Description: Category: Unreleased Structures

2023-01-11T05:56:56Z

New page: '''Unreleased structure''' The entry 8fo2 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8fo2 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8fo2 - Revision history

OCA at 11:01, 3 January 2024

OCA: Protected "8fo2" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8fo2 is ON HOLD Authors: Description: Category: Unreleased Structures