Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis

Cited 71 time in scopus
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Title
Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis
Author(s)
S Y Park; J E Park; T S Kim; Juhee Kim; M J Kwak; Bonsu Ku; L Tian; R N Murugan; M Ahn; S Komiya; H Hojo; N H Kim; Bo Yeon Kim; J K Bang; R L Erikson; K W Lee; Seung Jun Kim; B H Oh; W Yang; K S Lee
Bibliographic Citation
Nature Structural & Molecular Biology, vol. 21, no. 8, pp. 696-703
Publication Year
2014
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.
ISSN
1072-8368
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/nsmb.2846
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
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