The ribosomal RNA processing 1B:protein phosphatase 1 holoenzyme reveals non-canonical PP1 interaction motifs

Srivastava, Gautam; Bajaj, Rakhi; Kumar, Ganesan Senthil; Gaudreau-Lapierre, Antoine; Nicolas, Hannah; Chamousset, Delphine; Kreitler, Dale; Peti, Wolfgang; Trinkle-Mulcahy, Laura; Page, Rebecca

doi:10.1016/j.celrep.2022.111726

Title: The ribosomal RNA processing 1B:protein phosphatase 1 holoenzyme reveals non-canonical PP1 interaction motifs

Journal Article · Tue Nov 01 00:00:00 EDT 2022 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2022.111726· OSTI ID:2325409

Srivastava, Gautam; Bajaj, Rakhi; Kumar, Ganesan Senthil; Gaudreau-Lapierre, Antoine; Nicolas, Hannah; Chamousset, Delphine; Kreitler, Dale; Peti, Wolfgang; Trinkle-Mulcahy, Laura;

The serine/threonine protein phosphatase 1 (PP1) dephosphorylates hundreds of substrates by associating with >200 regulatory proteins to form specific holoenzymes. The major PP1 targeting protein in the nucleolus is RRP1B (ribosomal RNA processing 1B). In addition to selectively recruiting PP1β/PP1γ to the nucleolus, RRP1B also has a key role in ribosome biogenesis, among other functions. How RRP1B binds PP1 and regulates nucleolar phosphorylation signaling is not yet known. Here, we show that RRP1B recruits PP1 via established (RVxF/SILK/ΦΦ) and non-canonical motifs. These atypical interaction sites, the PP1β/γ specificity, and N-terminal AF-binding pockets rely on hydrophobic interactions that contribute to binding and, via phosphorylation, regulate complex formation. This work advances our understanding of PP1 isoform selectivity, reveals key roles of N-terminal PP1 residues in regulator binding, and suggests that additional PP1 interaction sites have yet to be identified, all of which are necessary for a systems biology understanding of PP1 function.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institute of General Medical Sciences; National Cancer Institute (NCI); National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke; Natural Sciences and Engineering Research Council

Grant/Contract Number:: AC02-06CH11357; R01NS091336; BER KP1607011; SC0012704; P30GM133893; KP1607011; ACB-12002; AGM-12006; P30GM138396; S10 OD012289; R01GM144483; 06674; 5018217; R01GM098482

OSTI ID:: 2325409

Alternate ID(s):: OSTI ID: 1922726

Report Number(s):: BNL-223950-2023-JAAM; S2211124722016047; 111726; PII: S2211124722016047

Journal Information:: Cell Reports, Journal Name: Cell Reports Vol. 41 Journal Issue: 9; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: Netherlands

Language:: English

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Title: The ribosomal RNA processing 1B:protein phosphatase 1 holoenzyme reveals non-canonical PP1 interaction motifs

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