Activation mechanism of PINK1.

ABSTRACT: Mutations in the protein kinase PINK1 lead to defects in mitophagy and cause autosomal recessive early onset Parkinson's disease^1,2. PINK1 has many unique features that enable it to phosphorylate ubiquitin and the ubiquitin-like domain of Parkin^3-9. Structural analysis of PINK1 from diverse insect species^10-12 with and without ubiquitin provided snapshots of distinct structural states yet did not explain how PINK1 is activated. Here we elucidate the activation mechanism of PINK1 using crystallography and cryo-electron microscopy (cryo-EM). A crystal structure of unphosphorylated Pediculus humanus corporis (Ph; human body louse) PINK1 resolves an N-terminal helix, revealing the orientation of unphosphorylated yet active PINK1 on the mitochondria. We further

SUBMITTER: Gan ZY 

PROVIDER: S-EPMC8828467 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature