TY - JOUR
T1 - Orientation and structure of the Ndc80 complex on the microtubule lattice
AU - Wilson-Kubalek, Elizabeth M.
AU - Cheeseman, Iain M.
AU - Yoshioka, Craig
AU - Desai, Arshad
AU - Milligan, Ronald A.
PY - 2008/9/22
Y1 - 2008/9/22
N2 - The four-subunit Ndc80 complex, comprised of Ndc80/Nuf2 and Spc24/Spc25 dimers, directly connects kinetochores to spindle microtubules. The complex is anchored to the kinetochore at the Spc24/25 end, and the Ndc80/Nuf2 dimer projects outward to bind to microtubules. Here, we use cryoelectron microscopy and helical image analysis to visualize the interaction of the Ndc80/Nuf2 dimer with microtubules. Our results, when combined with crystallography data, suggest that the globular domain of the Ndc80 subunit binds strongly at the interface between tubulin dimers and weakly at the adjacent intradimer interface along the protofilament axis. Such a binding mode, in which the Ndc80 complex interacts with sequential α/β-tubulin heterodimers, may be important for stabilizing kinetochore-bound microtubules. Additionally, we define the binding of the Ndc80 complex relative to microtubule polarity, which reveals that the microtubule interaction surface is at a considerable distance from the opposite kinetochore-anchored end; this binding geometry may facilitate polymerization and depolymerization at kinetochore-attached microtubule ends.
AB - The four-subunit Ndc80 complex, comprised of Ndc80/Nuf2 and Spc24/Spc25 dimers, directly connects kinetochores to spindle microtubules. The complex is anchored to the kinetochore at the Spc24/25 end, and the Ndc80/Nuf2 dimer projects outward to bind to microtubules. Here, we use cryoelectron microscopy and helical image analysis to visualize the interaction of the Ndc80/Nuf2 dimer with microtubules. Our results, when combined with crystallography data, suggest that the globular domain of the Ndc80 subunit binds strongly at the interface between tubulin dimers and weakly at the adjacent intradimer interface along the protofilament axis. Such a binding mode, in which the Ndc80 complex interacts with sequential α/β-tubulin heterodimers, may be important for stabilizing kinetochore-bound microtubules. Additionally, we define the binding of the Ndc80 complex relative to microtubule polarity, which reveals that the microtubule interaction surface is at a considerable distance from the opposite kinetochore-anchored end; this binding geometry may facilitate polymerization and depolymerization at kinetochore-attached microtubule ends.
UR - http://www.scopus.com/inward/record.url?scp=52249087768&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52249087768&partnerID=8YFLogxK
U2 - 10.1083/jcb.200804170
DO - 10.1083/jcb.200804170
M3 - Article
C2 - 18794333
AN - SCOPUS:52249087768
SN - 0021-9525
VL - 182
SP - 1055
EP - 1061
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -