The structure of SDS22 provides insights into the mechanism of heterodimer formation with PP1. Issue 12 (4th December 2018)

• Record Type: Journal Article
• Authors: Choy, Meng S.; Bolik-Coulon, Nicolas; Archuleta, Tara L.; Peti, Wolfgang; Page, Rebecca
• Is Part Of: Acta crystallographica. Volume 74:Issue 12(2018:Dec.)
• Page Start: 817
• Page End: 824
• Publication Date: 2018-12-04
• Subjects: SDS22 -- protein phosphatase 1 -- LRR protein -- PP1 regulator; Crystallography -- Periodicals; Crystals -- Periodicals; 548
• DOI: 10.1107/S2053230X18016503
• Languages: English
• ISSNs: 2053-230X

Abstract

Abstract : SDS22 is an ancient protein phosphatase 1 (PP1) regulatory protein that associates with PP1 at kinetochores and regulates PP1‐mediated dephosphorylation of Aurora B kinase. Here, the crystal structure of human SDS22 in a P 21 21 21 crystal form reveals that this leucine‐rich repeat protein is highly curved, resulting in distinct surfaces that are likely to be important for PP1 binding. Abstract : Protein phosphatase 1 (PP1) dephosphorylates hundreds of key biological targets by associating with nearly 200 regulatory proteins to form highly specific holoenzymes. The vast majority of regulators are intrinsically disordered proteins (IDPs) and bind PP1 via short linear motifs within their intrinsically disordered regions. One of the most ancient PP1 regulators is SDS22, a protein that is conserved from yeast to mammals. Sequence analysis of SDS22 revealed that it is a leucine‐rich repeat (LRR) protein, suggesting that SDS22, unlike nearly every other known PP1 regulator, is not an IDP but instead is fully structured. Here, the 2.9 Å resolution crystal structure of human SDS22 in space group P 21 21 21 is reported. SDS22 adopts an LRR fold with the horseshoe‐like curvature typical for this family of proteins. The structure results in surfaces with distinct chemical characteristics that are likely to be critical for PP1 binding.