The Ndc80/HEC1 complex is a contact point for kinetochore-microtubule attachment

被引:266
作者
Wei, Ronnie R.
Al-Bassam, Jawdat
Harrison, Stephen C.
机构
[1] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
关键词
D O I
10.1038/nsmb1186
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Kinetochores are multicomponent assemblies that connect chromosomal centromeres to mitotic-spindle microtubules. The Ndc80 complex is an essential core element of kinetochores, conserved from yeast to humans. It is a rod-like assembly of four proteins-Ndc80p (HEC1 in humans), Nuf2p, Spc24p and Spc25p. We describe here the crystal structure of the most conserved region of HEC1, which lies at one end of the rod and near the N terminus of the polypeptide chain. It folds into a calponin-homology domain, resembling the microtubule-binding domain of the plus-end-associated protein EB1. We show that an Ndc80p-Nuf2p heterodimer binds microtubules in vitro. The less conserved, N-terminal segment of Ndc80p contributes to the interaction and may be a crucial regulatory element. We propose that the Ndc80 complex forms a direct link between kinetochore core components and spindle microtubules.
引用
收藏
页码:54 / 59
页数:6
相关论文
共 50 条
[1]   Crystal structure of the actin-binding domain of α-actinin 1:: Evaluating two competing actin-binding models [J].
Borrego-Diaz, Emma ;
Kerff, Frederic ;
Lee, Sung Haeng ;
Ferron, Francois ;
Li, Yu ;
Dominguez, Roberto .
JOURNAL OF STRUCTURAL BIOLOGY, 2006, 155 (02) :230-238
[2]   The conserved KMN network constitutes the core microtubule-binding site of the kinetochore [J].
Cheeseman, Iain M. ;
Chappie, Joshua S. ;
Wilson-Kubalek, Elizabeth M. ;
Desai, Arshad .
CELL, 2006, 127 (05) :983-997
[3]   Phospho-regulation of kinetochore-microtubule attachments by the aurora kinase Ipl1p [J].
Cheeseman, LM ;
Anderson, S ;
Jwa, M ;
Green, EM ;
Kang, JS ;
Yates, JR ;
Chan, CSM ;
Drubin, DG ;
Barnes, G .
CELL, 2002, 111 (02) :163-172
[4]   Multiple sequence alignment with the Clustal series of programs [J].
Chenna, R ;
Sugawara, H ;
Koike, T ;
Lopez, R ;
Gibson, TJ ;
Higgins, DG ;
Thompson, JD .
NUCLEIC ACIDS RESEARCH, 2003, 31 (13) :3497-3500
[5]   COMPOSITE MOTIFS AND REPEAT SYMMETRY IN S-POMBE CENTROMERES - DIRECT ANALYSIS BY INTEGRATION OF NOTL RESTRICTION SITES [J].
CHIKASHIGE, Y ;
KINOSHITA, N ;
NAKASEKO, Y ;
MATSUMOTO, T ;
MURAKAMI, S ;
NIWA, O ;
YANAGIDA, M .
CELL, 1989, 57 (05) :739-751
[6]   Architecture of the human Ndc80-Hec1 complex, a critical constituent of the outer kinetochore [J].
Ciferri, C ;
De Luca, J ;
Monzani, S ;
Ferrari, KJ ;
Ristic, D ;
Wyman, C ;
Stark, H ;
Kilmartin, J ;
Salmon, ED ;
Musacchio, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (32) :29088-29095
[7]   ISOLATION OF THE CENTROMERE-LINKED CDC10 GENE BY COMPLEMENTATION IN YEAST [J].
CLARKE, L ;
CARBON, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (04) :2173-2177
[8]   Centromeres and kinetochores: From epigenetics to mitotic checkpoint signaling [J].
Cleveland, DW ;
Mao, YH ;
Sullivan, KF .
CELL, 2003, 112 (04) :407-421
[9]   A 125-BASE-PAIR CEN6 DNA FRAGMENT IS SUFFICIENT FOR COMPLETE MEIOTIC AND MITOTIC CENTROMERE FUNCTIONS IN SACCHAROMYCES-CEREVISIAE [J].
COTTAREL, G ;
SHERO, JH ;
HIETER, P ;
HEGEMANN, JH .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (08) :3342-3349
[10]   Kinetochore microtubule dynamics and attachment stability are regulated by Hec1 [J].
DeLuca, Jennifer G. ;
Gall, Walter E. ;
Ciferri, Claudio ;
Cimini, Daniela ;
Musacchio, Andrea ;
Salmon, E. D. .
CELL, 2006, 127 (05) :969-982