RRC ID |
57437
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Author |
Chik JK, Moiseeva V, Goel PK, Meinen BA, Koldewey P, An S, Mellone BG, Subramanian L, Cho US.
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Title |
Structures of CENP-C cupin domains at regional centromeres reveal unique patterns of dimerization and recruitment functions for the inner pocket.
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Journal |
J Biol Chem
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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.
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Volume |
294(38)
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Pages |
14119-14134
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Published |
2019-9-20
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DOI |
10.1074/jbc.RA119.008464
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PII |
S0021-9258(20)32095-0
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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
|
Times Cited |
2
|
Resource |
Yeast |
FY24916
FY24917
FY24918
FY24919 |