title: Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis.
abstract: Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. We show 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 did 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.
authors.affiliation: 1] Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2] Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea. [3].
authors.forename: Suk-Youl
authors.initials: SY
authors.lastname: Park
authors.affiliation: 1] Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2].
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: 1] Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2].
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Kim
authors.affiliation: 1] Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. [2].
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 1] Department of Biological Sciences, KAIST Institute for Biocentury, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. [2].
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Kwak
authors.affiliation: 1] Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. [2].
authors.forename: Bonsu
authors.initials: B
authors.lastname: Ku
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Tian
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Republic of Korea.
authors.forename: Ravichandran N
authors.initials: RN
authors.lastname: Murugan
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Republic of Korea.
authors.forename: Mija
authors.initials: M
authors.lastname: Ahn
authors.affiliation: Department of Applied Biochemistry, Tokai University, Kanagawa, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Komiya
authors.affiliation: Institute for Protein Research, Osaka University, Osaka, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hojo
authors.affiliation: Department of Animal Sciences, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Nam-Hyung
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Republic of Korea.
authors.forename: Jeong K
authors.initials: JK
authors.lastname: Bang
authors.affiliation: Biological Laboratories, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Erikson
authors.affiliation: 1] Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea. [2] Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, KAIST Institute for Biocentury, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Byung-Ha
authors.initials: BH
authors.lastname: Oh
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002502:Centrioles / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009369:Neoplasms / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: C551028:CEP152 protein, human; D018797:Cell Cycle Proteins; C526596:Cep192 protein, human; D002868:Chromosomal Proteins, Non-Histone; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases