4wsf | pdb_00004wsf
Falafel EVH1 domain bound to CENP-C FIM
Structural highlights
FunctionPP4R3_DROME Regulatory subunit of serine/threonine-protein phosphatase 4. The probable PP4 complex Pp4-19C-PPP4R2r-flfl (PPP4C-PPP4R2-PPP4R3) is required to prevent caspase induced cell death (in vitro). May be involved in DNA damage repair. Key mediator specific for the localization of mira and associated cell fate determinants during both interphase and mitosis. Nuclear Flfl is required to exclude mira/pros from the nucleus when inefficiently bound to the cytoskeleton/cortex, whereas cytosolic or membrane-associated flfl is required for the cortical association and asymmetric localization of mira/pros/brat/stau at metaphase and anaphase.[1] [2] [3] Publication Abstract from PubMedThe cell division cycle requires tight coupling between protein phosphorylation and dephosphorylation. However, understanding the cell cycle roles of multimeric protein phosphatases has been limited by the lack of knowledge of how their diverse regulatory subunits target highly conserved catalytic subunits to their sites of action. Phosphoprotein phosphatase 4 (PP4) has been recently shown to participate in the regulation of cell cycle progression. We now find that the EVH1 domain of the regulatory subunit 3 of Drosophila PP4, Falafel (Flfl), directly interacts with the centromeric protein C (CENP-C). Unlike other EVH1 domains that interact with proline-rich ligands, the crystal structure of the Flfl amino-terminal EVH1 domain bound to a CENP-C peptide reveals a new target-recognition mode for the phosphatase subunit. We also show that binding of Flfl to CENP-C is required to bring PP4 activity to centromeres to maintain CENP-C and attached core kinetochore proteins at chromosomes during mitosis. Centromeric binding and activity of Protein Phosphatase 4.,Lipinszki Z, Lefevre S, Savoian MS, Singleton MR, Glover DM, Przewloka MR Nat Commun. 2015 Jan 6;6:5894. doi: 10.1038/ncomms6894. PMID:25562660[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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