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Binding of the concave surface of the Sds22 superhelix to the alpha 4/alpha 5/alpha 6-triangle of protein phosphatase-1

Functional studies of the protein phosphatase-1 (PP1) regulator Sds22 suggest that it is indirectly and/or directly involved in one of the most ancient functions of PP1, i.e. reversing phosphorylation by the Aurora-related protein kinases. We predict that the conserved portion of Sds22 folds into a...

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Published in:The Journal of biological chemistry 2002-12, Vol.277 (49), p.47331
Main Authors: Ceulemans, Hugo, Vulsteke, Veerle, De Maeyer, Marc, Tatchell, Kelly, Stalmans, Willy, Bollen, Mathieu
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container_issue 49
container_start_page 47331
container_title The Journal of biological chemistry
container_volume 277
creator Ceulemans, Hugo
Vulsteke, Veerle
De Maeyer, Marc
Tatchell, Kelly
Stalmans, Willy
Bollen, Mathieu
description Functional studies of the protein phosphatase-1 (PP1) regulator Sds22 suggest that it is indirectly and/or directly involved in one of the most ancient functions of PP1, i.e. reversing phosphorylation by the Aurora-related protein kinases. We predict that the conserved portion of Sds22 folds into a curved superhelix and demonstrate that mutation to alanine of any of eight residues (Asp(148), Phe(170), Glu(192), Phe(214), Asp(280), Glu(300), Trp(302), or Tyr(327)) at the concave surface of this superhelix thwarts the interaction with PP1. Furthermore, we show that all mammalian isoforms of PP1 have the potential to bind Sds22. Interaction studies with truncated versions of PP1 and with chimeric proteins comprising fragments of PP1 and the yeast PP1-like protein phosphatase Ppz1 suggest that the site(s) required for the binding of Sds22 reside between residues 43 and 173 of PP1gamma(1). Within this region, a major interaction site was mapped to a triangular region delineated by the alpha4-, alpha5-, and alpha6-helices. Our data also show that well known regulatory binding sites of PP1, such as the RVXF-binding channel, the beta12/beta13-loop, and the acidic groove, are not essential for the interaction with Sds22.
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subjects Amino Acid Sequence
Animals
beta-Galactosidase - metabolism
Binding Sites
Blotting, Western
Catalytic Domain
Cell Cycle Proteins - chemistry
Cell Cycle Proteins - metabolism
Conserved Sequence
COS Cells
Databases as Topic
Gene Deletion
Models, Molecular
Molecular Sequence Data
Mutation
Nuclear Proteins
Phosphoprotein Phosphatases - chemistry
Phosphoprotein Phosphatases - metabolism
Plasmids - metabolism
Precipitin Tests
Protein Binding
Protein Folding
Protein Isoforms
Protein Phosphatase 1
Protein Structure, Tertiary
Rabbits
Rats
Sequence Homology, Amino Acid
Two-Hybrid System Techniques
title Binding of the concave surface of the Sds22 superhelix to the alpha 4/alpha 5/alpha 6-triangle of protein phosphatase-1
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