7lht: Difference between revisions
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==Structure of the LRRK2 dimer== | |||
<StructureSection load='7lht' size='340' side='right'caption='[[7lht]], [[Resolution|resolution]] 3.50Å' scene=''> | |||
== 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> | |||
</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='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> | |||
</table> | |||
<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> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7lht" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[LRRK2 3D structures|LRRK2 3D structures]] | |||
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__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]] | |||
