PUBLICATION
Structural basis for the inhibition of Polo-like kinase 1
- Authors
- Xu, J., Shen, C., Wang, T., Quan, J.
- ID
- ZDB-PUB-230620-79
- Date
- 2013
- Source
- Nature structural & molecular biology 20: 104710531047-53 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Catalytic Domain
- Cell Cycle Proteins/antagonists & inhibitors*
- Cell Cycle Proteins/chemistry*
- Cell Cycle Proteins/genetics
- Crystallography, X-Ray
- Drosophila Proteins/chemistry*
- Drosophila Proteins/genetics
- Humans
- Microtubule-Associated Proteins/chemistry*
- Microtubule-Associated Proteins/genetics
- Models, Biological
- Models, Molecular
- Molecular Sequence Data
- Multiprotein Complexes/chemistry
- Multiprotein Complexes/genetics
- Protein Conformation
- Protein Interaction Domains and Motifs
- Protein Serine-Threonine Kinases/antagonists & inhibitors*
- Protein Serine-Threonine Kinases/chemistry*
- Protein Serine-Threonine Kinases/genetics
- Proto-Oncogene Proteins/antagonists & inhibitors*
- Proto-Oncogene Proteins/chemistry*
- Proto-Oncogene Proteins/genetics
- Sequence Homology, Amino Acid
- Zebrafish Proteins/antagonists & inhibitors*
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- PubMed
- 23893132 Full text @ Nat. Struct. Mol. Biol.
Citation
Xu, J., Shen, C., Wang, T., Quan, J. (2013) Structural basis for the inhibition of Polo-like kinase 1. Nature structural & molecular biology. 20:104710531047-53.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping