Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis
| Autor: | Kyung S. Lee, Shinobu Komiya, Mija Ahn, Nam Kim, Bonsu Ku, Tae Sung Kim, Suk Youl Park, Seung Jun Kim, Jung-Eun Park, Ju Hee Kim, Jeong K. Bang, Ki Won Lee, Byung-Ha Oh, Wei Yang, Lan Tian, Raymond L. Erikson, Bo Yeon Kim, Mi Jeong Kwak, Hironobu Hojo, Ravichandran N. Murugan |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular PLK4 Centriole Chromosomal Proteins Non-Histone sports Molecular Sequence Data Mutation Missense Cell Cycle Proteins Centrosome cycle Protein Serine-Threonine Kinases Biology Crystallography X-Ray Protein Structure Secondary Article Chromosome segregation Procentriole Protein structure Structural Biology Neoplasms Humans Protein Interaction Domains and Motifs Amino Acid Sequence Protein Structure Quaternary Molecular Biology Peptide sequence Centrioles Hydrogen Bonding Cell biology sports.league HEK293 Cells Biogenesis HeLa Cells Protein Binding |
| Zdroj: | Nature structural & molecular biology |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. Here we showed that Plk4 relocalizes from the inner Cep192 ring to the outer Cep152 ring as newly recruited Cep152 assembles around the Cep192-encircled daughter centriole. Crystal structure analyses revealed that Cep192 - and Cep152-derived peptides bind the cryptic polo box (CPB) of Plk4 in opposite orientations and in a mutually exclusive manner. The Cep152-peptide bound to the CPB markedly better than the Cep192-peptide and effectively snatched the CPB away from a preformed CPB–Cep192-peptide complex. A cancer-associated Cep152 mutation impairing the Plk4 interaction induced defects in procentriole assembly and chromosome segregation. Thus, Plk4 is intricately regulated in time and space through ordered interactions with two distinct scaffolds, Cep192 and Cep152, and a failure in this process may lead to human cancer. |
| Databáze: | OpenAIRE |
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