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bioRxiv · 10.1101/2021.08.05.455304

Structure of PINK1 reveals autophosphorylation dimer and provides insights into binding to the TOM complex

Rasool, S.·Veyron, S.·Soya, N.·Eldeeb, M.·Lukacs, G.·Fon, E. A.·Trempe, J.-F.
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Abstract

Mutations in PINK1 causes autosomal-recessive Parkinsons disease. Mitochondrial damage results in PINK1 import arrest on the Translocase of the Outer Mitochondrial Membrane (TOM) complex, resulting in the activation of its ubiquitin kinase activity by autophosphorylation and initiation of Parkin-dependent mitochondrial clearance. Herein we report crystal structures of the entire cytosolic domain of insect PINK1. Our structures reveal a dimeric autophosphorylation complex targeting phosphorylation at the invariant Ser205 (human Ser228). The dimer interface requires insert 2, which is unique to PINK1. The structures also reveal how an N-terminal helix binds to the C-terminal extension and provide insights into stabilization of PINK1 on the core TOM complex.

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Rasool, S., Veyron, S., Soya, N., Eldeeb, M., Lukacs, G., Fon, E. A., Trempe, J.-F.. 2021-08-05. Structure of PINK1 reveals autophosphorylation dimer and provides insights into binding to the TOM complex. https://doi.org/10.1101/2021.08.05.455304

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