| Literature DB >> 27499294 |
Jonathan A Stefely1, Floriana Licitra2, Leila Laredj2, Andrew G Reidenbach1, Zachary A Kemmerer1, Anais Grangeray3, Tiphaine Jaeg-Ehret2, Catherine E Minogue4, Arne Ulbrich4, Paul D Hutchins4, Emily M Wilkerson4, Zheng Ruan5, Deniz Aydin6, Alexander S Hebert7, Xiao Guo8, Elyse C Freiberger9, Laurence Reutenauer2, Adam Jochem10, Maya Chergova2, Isabel E Johnson1, Danielle C Lohman1, Matthew J P Rush4, Nicholas W Kwiecien4, Pankaj K Singh2, Anna I Schlagowski11, Brendan J Floyd1, Ulrika Forsman12, Pavel J Sindelar13, Michael S Westphall7, Fabien Pierrel14, Joffrey Zoll11, Matteo Dal Peraro6, Natarajan Kannan5, Craig A Bingman9, Joshua J Coon15, Philippe Isope3, Hélène Puccio16, David J Pagliarini17.
Abstract
The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates, functions that are likely conserved across all domains of life. Collectively, our results lend insight into the molecular activities of the ancient UbiB family and elucidate the biochemical underpinnings of a human disease.Entities:
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Year: 2016 PMID： 27499294 PMCID： PMC5012427 DOI： 10.1016/j.molcel.2016.06.030
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970