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PMID: 14592974 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

The crystal structure of the human polo-like kinase-1 polo box domain and its phospho-peptide complex.

The EMBO journal ·Vol. 22 ·No. 21 ·2003-11-03 ·Pages 5757-68

Cheng KY, Lowe ED, Sinclair J, Nigg EA, Johnson LN

Abstract

Human polo-like kinase Plk1 localizes to the centrosomes, kinetochores and central spindle structures during mitosis. It plays an essential role in promoting mitosis and cytokinesis through phosphorylation of a number of different substrates. Kinase activity is regulated by a conserved C-terminal domain, termed the polo box domain (PBD), which acts both as an autoinhibitory domain and as a subcellular localization domain. We have determined the crystal structure of Plk1 PBD (residues 367-603) to 2.2 A resolution and the structure of a phospho-peptide-PBD (residues 345-603) complex to 2.3 A resolution. The two polo boxes of the PBD exhibit identical folds based on a six-stranded beta-sheet and an alpha-helix, despite only 12% sequence identity. The phospho-peptide binds at a site between the two polo boxes. It makes a short antiparallel beta-sheet connection and critical contacts to residues Trp414, Leu490, His538 and Lys540. Most of these residues had been shown to be important for biological activity through mutational studies. The results provide an explanation for phospho-peptide recognition and create the basis for new functional studies.

MeSH Terms
Amino Acid Sequence Cell Cycle Proteins Crystallography, X-Ray Humans Macromolecular Substances Models, Molecular Molecular Sequence Data Protein Folding Protein Kinases/chemistry,genetics Protein Serine-Threonine Kinases/chemistry,genetics Protein Structure, Secondary Protein Structure, Tertiary Proto-Oncogene Proteins Recombinant Proteins/chemistry,genetics Sequence Homology, Amino Acid Static Electricity
Chemicals
Cell Cycle Proteins Macromolecular Substances Proto-Oncogene Proteins Recombinant Proteins Protein Kinases PLK4 protein, human Protein Serine-Threonine Kinases polo-like kinase 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cheng Kin-Yip
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Lowe Edward D
Sinclair John
Nigg Erich A
Johnson Louise N
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg558
Published
2003-11-03
Pages
5757-68
Language
English
Region
England
NLM ID
8208664
PMCID
PMC275415
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg558 PMC Full Text View journal details
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