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PDBsum entry 2igp
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References listed in PDB file
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Key reference
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Title
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The ndc80/hec1 complex is a contact point for kinetochore-Microtubule attachment.
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Authors
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R.R.Wei,
J.Al-Bassam,
S.C.Harrison.
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Ref.
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Nat Struct Biol, 2007,
14,
54-59.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
(a) Ribbon diagram of HEC1_CH (HEC[81–196]). (b) View from
the opposite direction to a, showing the potential
microtubule-binding site, analogous to that on EB1. Side chains
of Arg84, Phe125, Tyr160, Phe162 and Tyr187 are shown as sticks.
(c) Ribbon diagram of EB1 microtubule-binding domain (PDB
1PA7)^24 in the same orientation as HEC1_CH in a. (d) EB1
microtubule-binding domain, in the same orientation as HEC1_CH
in b, showing the proposed microtubule-binding site^24. The side
chains of Lys89 and its surrounding hydrophobic residues are
shown as sticks, with O and N in red and blue, respectively. N
and C termini are labeled.
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Figure 2.
(a,b) Surface representations of HEC1_CH in the orientations
of Figure 1a,b, respectively, colored by degree of conservation
(dark blue, most conserved; white, least conserved), showing
that the potential microtubule-binding surface is conserved
across species. (c,d) Surface representations showing
electrostatic potential of HEC1_CH and EB1 microtubule-binding
domain, in the orientations of Figure 1b,d, respectively. Red to
blue, -15 k[b]T to +15 k[b]T, as calculated by Delphi^49. (e)
Multiple sequence alignment for Ndc80/HEC1 and EB1 CH domain
(bottom), generated with CLUSTAL W^50. Secondary structural
elements derived from the crystal structure are colored as in
Figure 1a. Number of initial residue for each homolog is shown
after species name. Residues are colored by degree of
conservation: white letters on dark blue background, identical;
blue on blue-gray, strongly conserved; light blue on white,
weakly conserved. Lys89 of EB1, which is required for
microtubule binding, is boxed in red.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2007,
14,
54-59)
copyright 2007.
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