5OAT

PINK1 structure

Summary for 5OAT

• Entry DOI: 10.2210/pdb5oat/pdb
• Descriptor: Serine/threonine-protein kinase PINK1, mitochondrial-like Protein, MAGNESIUM ION (3 entities in total)
• Functional Keywords: kinase for phosphorylation, kinase
• Biological source: Tribolium castaneum (Red flour beetle)
• Total number of polymer chains: 6
• Total formula weight: 279080.93

Authors

Kumar, A.,Tamjar, J.,Woodroof, H.I.,Raimi, O.G.,Waddell, A.Y.,Peggie, M.,Muqit, M.M.K.,van Aalten, D.M.F. (deposition date: 2017-06-23, release date: 2017-10-11, Last modification date: 2024-10-16)

Primary citation

Kumar, A.,Tamjar, J.,Waddell, A.D.,Woodroof, H.I.,Raimi, O.G.,Shaw, A.M.,Peggie, M.,Muqit, M.M.,van Aalten, D.M.
Structure of PINK1 and mechanisms of Parkinson's disease associated mutations.
Elife, 6:-, 2017

PubMed Abstract: Mutations in the human kinase PINK1 (hPINK1) are associated with autosomal recessive early-onset Parkinson's disease (PD). hPINK1 activates Parkin E3 ligase activity, involving phosphorylation of ubiquitin and the Parkin ubiquitin-like (Ubl) domain as yet poorly understood mechanisms. hPINK1 is unusual amongst kinases due to the presence of three loop insertions of unknown function. We report the structure of PINK1 (PINK1), revealing several unique extensions to the canonical protein kinase fold. The third insertion, together with autophosphorylation at residue Ser205, contributes to formation of a bowl-shaped binding site for ubiquitin. We also define a novel structural element within the second insertion that is held together by a distal loop that is critical for PINK1 activity. The structure of PINK1 explains how PD-linked mutations that lie within the kinase domain result in hPINK1 loss-of-function and provides a platform for the exploration of small molecule modulators of hPINK1.

PubMed: 28980524
DOI: 10.7554/eLife.29985

Experimental method

X-RAY DIFFRACTION (2.78 Å)