Structural basis for the inhibition of Polo-like kinase 1
Copyright policy )Structural basis for the inhibition of Polo-like kinase 1
Polo-like kinase 1 (PLK1) is a master regulator of mitosis and is considered a potential drug target for cancer therapy. PLK1 is characterized by an N-terminal kinase domain (KD) and a C-terminal Polo-box domain (PBD). The KD and PBD are mutually inhibited, but the molecular mechanisms of the autoinhibition remain unclear. Here we report the 2.3-Å crystal structure of the complex of the Danio rerio KD and PBD together with a PBD-binding motif of Drosophila melanogaster microtubule-associated protein 205 (Map205(PBM)). The structure reveals that the PBD binds and rigidifies the hinge region of the KD in a distinct conformation from that of the phosphopeptide-bound PBD. This structure provides a framework for understanding the autoinhibitory mechanisms of PLK1 and also sheds light on the activation mechanisms of PLK1 by phosphorylation or phosphopeptide binding.
- Peking University China (People's Republic of)
- Peking University China (People's Republic of)
Models, Molecular, Sequence Homology, Amino Acid, Protein Conformation, Molecular Sequence Data, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Zebrafish Proteins, Crystallography, X-Ray, Models, Biological, Polo-Like Kinase 1, Catalytic Domain, Multiprotein Complexes, Proto-Oncogene Proteins, Animals, Drosophila Proteins, Humans, Protein Interaction Domains and Motifs, Amino Acid Sequence, Microtubule-Associated Proteins
Models, Molecular, Sequence Homology, Amino Acid, Protein Conformation, Molecular Sequence Data, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Zebrafish Proteins, Crystallography, X-Ray, Models, Biological, Polo-Like Kinase 1, Catalytic Domain, Multiprotein Complexes, Proto-Oncogene Proteins, Animals, Drosophila Proteins, Humans, Protein Interaction Domains and Motifs, Amino Acid Sequence, Microtubule-Associated Proteins
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