8FAC
Structure of the leucine-rich repeat kinase 1 monomer
Summary for 8FAC
| Entry DOI | 10.2210/pdb8fac/pdb |
| EMDB information | 28949 28950 28951 |
| Descriptor | Leucine-rich repeat serine/threonine-protein kinase 1, GUANOSINE-5'-DIPHOSPHATE (2 entities in total) |
| Functional Keywords | kinase, lrrk, multi-domain protein, gtpase, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 229999.56 |
| Authors | Metcalfe, R.D.,Martinez Fiesco, J.A.,Zhang, P. (deposition date: 2022-11-25, release date: 2023-08-16) |
| Primary citation | 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 Cited by 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: 37558661DOI: 10.1038/s41467-023-40532-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.92 Å) |
Structure validation
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