Structures of CENP-C cupin domains at regional centromeres reveal unique patterns of dimerization and recruitment functions for the inner pocket.

Autor: Chik JK; Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109.; Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109., Moiseeva V; School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom., Goel PK; School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom., Meinen BA; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109., Koldewey P; Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109., An S; Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109., Mellone BG; Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut 06269., Subramanian L; School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom l.subramanian@qmul.ac.uk., Cho US; Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 uhnsoo@med.umich.edu.
Jazyk: angličtina
Zdroj: The Journal of biological chemistry [J Biol Chem] 2019 Sep 20; Vol. 294 (38), pp. 14119-14134. Date of Electronic Publication: 2019 Jul 31.
DOI: 10.1074/jbc.RA119.008464
Abstrakt: 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 Mif2 CENP-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 Cnp3 CENP-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.
(© 2019 Chik et al.)
Databáze: MEDLINE