Structural analysis of the full-length human LRRK2.
LRRK2
LRRK2 dimer
LRRK2 mutations
Parkinson's disease
kinase
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
24 06 2021
24 06 2021
Historique:
received:
05
01
2021
revised:
23
03
2021
accepted:
04
05
2021
pubmed:
10
6
2021
medline:
6
1
2022
entrez:
9
6
2021
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 34107286
pii: S0092-8674(21)00601-2
doi: 10.1016/j.cell.2021.05.004
pmc: PMC8887629
mid: NIHMS1775752
pii:
doi:
Substances chimiques
LRRK2 protein, human
EC 2.7.11.1
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3519-3527.e10Subventions
Organisme : NHLBI NIH HHS
ID : K99 HL143037
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS055077
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL143037
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG053987
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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