RRC ID 57437
著者 Chik JK, Moiseeva V, Goel PK, Meinen BA, Koldewey P, An S, Mellone BG, Subramanian L, Cho US.
タイトル Structures of CENP-C cupin domains at regional centromeres reveal unique patterns of dimerization and recruitment functions for the inner pocket.
ジャーナル J Biol Chem
Abstract The successful assembly and regulation of the kinetochore are critical for the equal and accurate segregation of genetic material during the cell cycle. CENP-C (centromere protein C), a conserved inner kinetochore component, has been broadly characterized as a scaffolding protein and is required for the recruitment of multiple kinetochore proteins to the centromere. At its C terminus, CENP-C harbors a conserved cupin domain that has an established role in protein dimerization. Although the crystal structure of the Saccharomyces cerevisiae Mif2CENP-C cupin domain has been determined, centromeric organization and kinetochore composition vary greatly between S. cerevisiae (point centromere) and other eukaryotes (regional centromere). Therefore, whether the structural and functional role of the cupin domain is conserved throughout evolution requires investigation. Here, we report the crystal structures of the Schizosaccharomyces pombe and Drosophila melanogaster CENP-C cupin domains at 2.52 and 1.81 Å resolutions, respectively. Although the central jelly roll architecture is conserved among the three determined CENP-C cupin domain structures, the cupin domains from organisms with regional centromeres contain additional structural features that aid in dimerization. Moreover, we found that the S. pombe Cnp3CENP-C jelly roll fold harbors an inner binding pocket that is used to recruit the meiosis-specific protein Moa1. In summary, our results unveil the evolutionarily conserved and unique features of the CENP-C cupin domain and uncover the mechanism by which it functions as a recruitment factor.
巻・号 294(38)
ページ 14119-14134
公開日 2019-9-20
DOI 10.1074/jbc.RA119.008464
PII S0021-9258(20)32095-0
PMID 31366733
PMC PMC6755791
MeSH Animals Cell Cycle Proteins / metabolism Centromere / metabolism Centromere Protein A / metabolism Chromosomal Proteins, Non-Histone / metabolism* Chromosomal Proteins, Non-Histone / ultrastructure* Crystallography, X-Ray / methods DNA-Binding Proteins / metabolism Dimerization Drosophila Proteins / metabolism Drosophila Proteins / ultrastructure Drosophila melanogaster / metabolism Histones / metabolism Kinetochores / metabolism Kinetochores / ultrastructure Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / metabolism
IF 4.106
引用数 2
リソース情報
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