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Kinetochore recruitment of CENP-F illustrates how paralog divergence shapes kinetochore composition and function

Authors :
Andrea Musacchio
Giuseppe Ciossani
Katharina Overlack
Huis in ‘t Veld P
Sabine Wohlgemuth
Stefano Maffini
Körner C
Arsen Petrovic
Publication Year :
2018
Publisher :
Cold Spring Harbor Laboratory, 2018.

Abstract

The metazoan proteins CENP-E and CENP-F are components of a fibrous layer of mitotic kinetochores named the corona. Several features suggest that CENP-E and CENP-F are paralogs: they are very large (approximately 2700 and 3200 residues, respectively), rich in predicted coiled-coil structure, C-terminally prenylated, and endowed with microtubule-binding sites at their termini. In addition, CENP-E contains an ATP-hydrolyzing motor domain that promotes microtubule plus-end directed motion. Here, we show that CENP-E and CENP- F are recruited to mitotic kinetochores independently of the Rod-Zwilch-ZW10 (RZZ) complex, the main corona constituent. We identify selective interactions of CENP-E and CENP-F respectively with BubR1 and Bub1, paralogous proteins involved in mitotic checkpoint control and chromosome alignment. While BubR1 is dispensable for kinetochore localization of CENP-E, Bub1 is stringently required for CENP-F localization. Through biochemical reconstitution, we demonstrate that the CENP-E:BubR1 and CENP-F:Bub1 interactions are direct and require similar determinants, a dimeric coiled-coil in CENP-E or CENP-F and a kinase domain in BubR1 or Bub1. Our findings are consistent with the existence of ‘pseudo-symmetric’, paralogous Bub1:CENP-F and BubR1:CENP-E axes, supporting evolutionary relatedness of CENP-E and CENP-F.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....3e5bdcb360d2889cb3bd1ae01621a735
Full Text :
https://doi.org/10.1101/276204