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Nat Commun. 2019 Apr 29;10(1):1977. doi: 10.1038/s41467-019-09952-x.

Conserved phosphorylation hotspots in eukaryotic protein domain families.

Author information

1
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
2
Institute of Medical Microbiology, University of Zurich, CH-8006, Zurich, Switzerland.
3
Institute of Biochemistry, ETH Zurich, CH-8093, Zurich, Switzerland.
4
European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany.
5
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.
6
BenevolentAI, London, NW1 1LW, UK.
7
Drosophila RNAi Screening Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.
8
Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.
9
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. pbeltrao@ebi.ac.uk.

Abstract

Protein phosphorylation is the best characterized post-translational modification that regulates almost all cellular processes through diverse mechanisms such as changing protein conformations, interactions, and localization. While the inventory for phosphorylation sites across different species has rapidly expanded, their functional role remains poorly investigated. Here, we combine 537,321 phosphosites from 40 eukaryotic species to identify highly conserved phosphorylation hotspot regions within domain families. Mapping these regions onto structural data reveals that they are often found at interfaces, near catalytic residues and tend to harbor functionally important phosphosites. Notably, functional studies of a phospho-deficient mutant in the C-terminal hotspot region within the ribosomal S11 domain in the yeast ribosomal protein uS11 shows impaired growth and defective cytoplasmic 20S pre-rRNA processing at 16 °C and 20 °C. Altogether, our study identifies phosphorylation hotspots for 162 protein domains suggestive of an ancient role for the control of diverse eukaryotic domain families.

PMID:
31036831
PMCID:
PMC6488607
DOI:
10.1038/s41467-019-09952-x
[Indexed for MEDLINE]
Free PMC Article

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