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Protein AMPylation by an Evolutionarily Conserved Pseudokinase

Sreelatha, Anju and Yee, Samantha and Lopez-Garrido, Javier and Park, Sangwoo and Kinch, Lisa and Pilch, Sylwia and Servage, Kelly and Zhang, Junmei and Jiou, Jenny and Karasiewicz, Monika and Łobocka, Małgorzata and Grishin, Nick and Orth, Kim and Kucharczyk, Roza and Pawłowski, Krzysztof and Tomchik, Diana and Tagliabracci, Vincent (2018) Protein AMPylation by an Evolutionarily Conserved Pseudokinase. Cell, S0092 (18). pp. 31107-31113. ISSN 0092-8674

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Official URL: https://www.ncbi.nlm.nih.gov/pubmed/30270044

Abstract

Approximately 10% of human protein kinases are believed to be inactive and named pseudokinases because they lack residues required for catalysis. Here, we show that the highly conserved pseudokinase selenoprotein-O (SelO) transfers AMP from ATP to Ser, Thr, and Tyr residues on protein substrates (AMPylation), uncovering a previously unrecognized activity for a member of the protein kinase superfamily. The crystal structure of a SelO homolog reveals a protein kinase-like fold with ATP flipped in the active site, thus providing a structural basis for catalysis. SelO pseudokinases localize to the mitochondria and AMPylate proteins involved in redox homeostasis. Consequently, SelO activity is necessary for the proper cellular response to oxidative stress. Our results suggest that AMPylation may be a more widespread post-translational modification than previously appreciated and that pseudokinases should be analyzed for alternative transferase activities.

Item Type:Article
Subjects:Q Science > Q Science (General)
Q Science > QD Chemistry
Divisions:Department of Genetics
ID Code:1189
Deposited By: Dr hab Roza Kucharczyk
Deposited On:19 Oct 2018 13:40
Last Modified:19 Oct 2018 14:15

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