8FAC

Structure of the leucine-rich repeat kinase 1 monomer

8FAC の概要

• エントリーDOI: 10.2210/pdb8fac/pdb
• EMDBエントリー: 28949 28950 28951
• 分子名称: Leucine-rich repeat serine/threonine-protein kinase 1, GUANOSINE-5'-DIPHOSPHATE (2 entities in total)
• 機能のキーワード: kinase, lrrk, multi-domain protein, gtpase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 229999.56

構造登録者

Metcalfe, R.D.,Martinez Fiesco, J.A.,Zhang, P. (登録日: 2022-11-25, 公開日: 2023-08-16)

主引用文献

Metcalfe, R.D.,Martinez Fiesco, J.A.,Bonet-Ponce, L.,Kluss, J.H.,Cookson, M.R.,Zhang, P.
Structure and regulation of full-length human leucine-rich repeat kinase 1.
Nat Commun, 14:4797-4797, 2023

PubMed Abstract: The human leucine-rich repeat kinases (LRRKs), LRRK1 and LRRK2 are large and unusually complex multi-domain kinases, which regulate fundamental cellular processes and have been implicated in human disease. Structures of LRRK2 have recently been determined, but the structure and molecular mechanisms regulating the activity of the LRRK1 as well as differences in the regulation of LRRK1 and LRRK2 remain unclear. Here, we report a cryo-EM structure of the LRRK1 monomer and a lower-resolution cryo-EM map of the LRRK1 dimer. The monomer structure, in which the kinase is in an inactive conformation, reveals key interdomain interfaces that control kinase activity as we validate experimentally. Both the LRRK1 monomer and dimer are structurally distinct compared to LRRK2. Overall, our results provide structural insights into the activation of the human LRRKs, which advance our understanding of their physiological and pathological roles.

PubMed: 37558661
DOI: 10.1038/s41467-023-40532-2

実験手法

ELECTRON MICROSCOPY (3.92 Å)