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2016 ; 167
(4
): 1028-1040.e15
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gab.com Text
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Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C
at Human Kinetochores
#MMPMID27881301
Petrovic A
; Keller J
; Liu Y
; Overlack K
; John J
; Dimitrova YN
; Jenni S
; van Gerwen S
; Stege P
; Wohlgemuth S
; Rombaut P
; Herzog F
; Harrison SC
; Vetter IR
; Musacchio A
Cell
2016[Nov]; 167
(4
): 1028-1040.e15
PMID27881301
show ga
Kinetochores, multisubunit protein assemblies, connect chromosomes to spindle
microtubules to promote chromosome segregation. The 10-subunit KMN assembly
(comprising KNL1, MIS12, and NDC80 complexes, designated KNL1C, MIS12C, and
NDC80C) binds microtubules and regulates mitotic checkpoint function through
NDC80C and KNL1C, respectively. MIS12C, on the other hand, connects the KMN to
the chromosome-proximal domain of the kinetochore through a direct interaction
with CENP-C. The structural basis for this crucial bridging function of MIS12C is
unknown. Here, we report crystal structures of human MIS12C associated with a
fragment of CENP-C and unveil the role of Aurora B kinase in the regulation of
this interaction. The structure of MIS12:CENP-C complements previously determined
high-resolution structures of functional regions of NDC80C and KNL1C and
allows us to build a near-complete structural model of the KMN assembly. Our work
illuminates the structural organization of essential chromosome segregation
machinery that is conserved in most eukaryotes.