8smc: Difference between revisions

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'''Unreleased structure'''


The entry 8smc is ON HOLD
==Cryo-EM structure of LRRK2 bound with type-I inhibitor DNL201==
<StructureSection load='8smc' size='340' side='right'caption='[[8smc]], [[Resolution|resolution]] 4.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8smc]] is a 1 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=8SMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SMC 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]] 4.02&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=TVT:2-methyl-2-(3-methyl-4-{[4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-1H-pyrazol-1-yl)propanenitrile'>TVT</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=8smc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8smc OCA], [https://pdbe.org/8smc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8smc RCSB], [https://www.ebi.ac.uk/pdbsum/8smc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8smc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q17RV3_HUMAN Q17RV3_HUMAN]
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 8smc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Sun J]]
[[Category: Zhu H]]
Retrieved from "https://proteopedia.org/8smc"