Protein AMPylation by an Evolutionarily Conserved Pseudokinase

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 (AM...

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Vydáno v:Cell Ročník 175; číslo 3; s. 809
Hlavní autoři: Sreelatha, Anju, Yee, Samantha S, Lopez, Victor A, Park, Brenden C, Kinch, Lisa N, Pilch, Sylwia, Servage, Kelly A, Zhang, Junmei, Jiou, Jenny, Karasiewicz-Urbańska, Monika, Łobocka, Małgorzata, Grishin, Nick V, Orth, Kim, Kucharczyk, Roza, Pawłowski, Krzysztof, Tomchick, Diana R, Tagliabracci, Vincent S
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 18.10.2018
Témata:
Adenosine Monophosphate - metabolism
Catalytic Domain
Conserved Sequence
Humans
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Oxidative Stress
Protein Processing, Post-Translational
Selenoproteins - chemistry
Selenoproteins - metabolism
SELENOO
selenocysteine
adenylylation
glutathionylation
glutaredoxin
kinase structure
oxidative stress
ISSN:1097-4172, 1097-4172
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2018.08.046