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PMID: 12853468 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

The structure of the cell cycle protein Cdc14 reveals a proline-directed protein phosphatase.

The EMBO journal ·Vol. 22 ·No. 14 ·2003-07-15 ·Pages 3524-35

Gray CH, Good VM, Tonks NK, Barford D

Abstract

The Cdc14 family of dual-specificity protein phosphatases (DSPs) is conserved within eukaryotes and functions to down-regulate mitotic Cdk activities, promoting cytokinesis and mitotic exit. We have integrated structural and kinetic analyses to define the molecular mechanism of the dephosphorylation reaction catalysed by Cdc14. The structure of Cdc14 illustrates a novel arrangement of two domains, each with a DSP-like fold, arranged in tandem. The C-terminal domain contains the conserved PTP motif of the catalytic site, whereas the N-terminal domain, which shares no sequence similarity with other DSPs, contributes to substrate specificity, and lacks catalytic activity. The catalytic site is located at the base of a pronounced surface channel formed by the interface of the two domains, and regions of both domains interact with the phosphopeptide substrate. Specificity for a pSer-Pro motif is mediated by a hydrophobic pocket that is capable of accommodating the apolar Pro(P+1) residue of the peptide. Our structural and kinetic data support a role for Cdc14 in the preferential dephosphorylation of proteins modified by proline-directed kinases.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Catalytic Domain Cell Cycle Proteins/chemistry Conserved Sequence Crystallography, X-Ray Humans Kinetics Models, Molecular Molecular Sequence Data Phosphoprotein Phosphatases/isolation & purification,metabolism Proline/chemistry Protein Conformation Protein Folding Protein Structure, Secondary Protein Structure, Tertiary Protein Tyrosine Phosphatases/chemistry Saccharomyces cerevisiae Proteins/chemistry Sequence Homology, Amino Acid Substrate Specificity
Chemicals
CDC14 protein, S cerevisiae Cell Cycle Proteins Saccharomyces cerevisiae Proteins Proline Phosphoprotein Phosphatases Protein Tyrosine Phosphatases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Gray Christopher H
Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
Good Valerie M
Tonks Nicholas K
Barford David
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg348
Published
2003-07-15
Pages
3524-35
Language
English
Region
England
NLM ID
8208664
PMCID
PMC165618
Subset
IM
Databases
PDB
1OHC, 1OHD, 1OHE
External Links
PubMed source DOI: 10.1093/emboj/cdg348 PMC Full Text View journal details
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