Structure-Guided Exploration of SDS22 Interactions with Protein Phosphatase PP1 and the Splicing Factor BCLAF1

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2019 Jan 22

PMID 30661852

Citations 9

Authors

Ewald Heroes

Gerd Van der Hoeven

Meng S Choy

Javier Del Pino Garcia

Monica Ferreira

Mieke Nys

Rita Derua

Monique Beullens

Chris Ulens

Wolfgang Peti

Luc Van Meervelt

Rebecca Page

Mathieu Bollen

Affiliations

Soon will be listed here.

Abstract

SDS22 is an ancient regulator of protein phosphatase-1 (PP1). Our crystal structure of SDS22 shows that its twelve leucine-rich repeats adopt a banana-shaped fold that is shielded from solvent by capping domains at its extremities. Subsequent modeling and biochemical studies revealed that the concave side of SDS22 likely interacts with PP1 helices α5 and α6, which are distal from the binding sites of many previously described PP1 interactors. Accordingly, we found that SDS22 acts as a "third" subunit of multiple PP1 holoenzymes. The crystal structure of SDS22 also revealed a large basic surface patch that enables binding of a phosphorylated form of splicing factor BCLAF1. Taken together, our data provide insights into the formation of PP1:SDS22 and the recruitment of additional interaction proteins, such as BCLAF1.

Citing Articles

Identification of phosphatases that dephosphorylate the co-chaperone BAG3.

Kokot T, Zimmermann J, Chand Y, Krier F, Reimann L, Scheinost L Life Sci Alliance. 2024; 8(2).

PMID: 39562141 PMC: 11576475. DOI: 10.26508/lsa.202402734.

Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases.

Kueck A, Boom J, Koska S, Ron D, Meyer H Proc Natl Acad Sci U S A. 2024; 121(36):e2408787121.

PMID: 39207734 PMC: 11388335. DOI: 10.1073/pnas.2408787121.

SDS22 coordinates the assembly of holoenzymes from nascent protein phosphatase-1.

Cao X, Lake M, Van der Hoeven G, Claes Z, Del Pino Garcia J, Lemaire S Nat Commun. 2024; 15(1):5359.

PMID: 38918402 PMC: 11199634. DOI: 10.1038/s41467-024-49746-4.

Inhibitor-3 inhibits Protein Phosphatase 1 via a metal binding dynamic protein-protein interaction.

Srivastava G, Choy M, Bolik-Coulon N, Page R, Peti W Nat Commun. 2023; 14(1):1798.

PMID: 37002212 PMC: 10066265. DOI: 10.1038/s41467-023-37372-5.

leucine-rich repeat protein 1 downregulates protein phosphatase 1 activity and is required for efficient oocyst development.

Freville A, Gnangnon B, Tremp A, De Witte C, Cailliau K, Martoriati A Open Biol. 2022; 12(8):220015.

PMID: 35920043 PMC: 9346556. DOI: 10.1098/rsob.220015.

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