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* Residue conservation analysis
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Enzyme class:
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Chains A, B:
E.C.?
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DOI no:
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Structure
14:1003-1009
(2006)
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PubMed id:
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Structure of a central component of the yeast kinetochore: the Spc24p/Spc25p globular domain.
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R.R.Wei,
J.R.Schnell,
N.A.Larsen,
P.K.Sorger,
J.J.Chou,
S.C.Harrison.
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ABSTRACT
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The Ndc80 complex, a kinetochore component conserved from yeast to humans, is
essential for proper chromosome alignment and segregation during mitosis. It is
an approximately 570 A long, rod-shaped assembly of four proteins--Ndc80p
(Hec1), Nuf2p, Spc24p, and Spc25p--with globular regions at either end of a
central shaft. The complex bridges from the centromere-proximal inner
kinetochore layer at its Spc24/Spc25 globular end to the microtubule binding
outer kinetochore layer at its Ndc80/Nuf2 globular end. We report the atomic
structures of the Spc24/Spc25 globular domain, determined both by X-ray
crystallography at 1.9 A resolution and by NMR. Spc24 and Spc25 fold tightly
together into a single globular entity with pseudo-2-fold symmetry. Conserved
residues line a common hydrophobic core and the bottom of a cleft, indicating
that the functional orthologs from other eukaryotes will have the same structure
and suggesting a docking site for components of the inner kinetochore.
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Selected figure(s)
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Figure 1.
Figure 1. Schematic Diagram of the Ndc80 Complex MT,
microtubule; CEN, centromere. Each subunit is represented by an
oval (the globular domain) and a stick (the coiled-coil region).
The coiled-coils of Ndc80p/Nuf2p and Spc24p/Spc25p form the
shaft. The globular domains of Ndc80p/Nuf2p form the “outer”
head, which faces the microtubule; the globular domains of the
Spc24p/Spc25p, the “inner” head, which faces the centromere.
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Figure 2.
Figure 2. Overview of the NMR and Crystal Structures of
Spc24G/Spc25G (A) Superposition of the backbones of the
solution NMR structure (light blue) and crystal structure
(gold). The dotted lines represent unstructured residues
138–154 of Spc24G and 128–132 of Spc25G. The N and C termini
of Spc24G and Spc25G are labeled with “ 24N,” “24C,”
“25N,” and “25C,” respectively. (B) Ribbon diagram
of the crystal structure in the same view as in (A). The α
helices and β strands are orange and yellow in Spc24G and green
and blue in Spc25G, respectively. (C) Folding diagram of
Spc24G and Spc25G. The secondary structures are colored as in
(B). The N and C termini are labeled with “N” and “C,”
respectively.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2006,
14,
1003-1009)
copyright 2006.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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E.A.Foley,
and
T.M.Kapoor
(2012).
Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore.
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Nat Rev Mol Cell Biol,
14,
25-37.
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G.M.Alushin,
V.Musinipally,
D.Matson,
J.Tooley,
P.T.Stukenberg,
and
E.Nogales
(2012).
Multimodal microtubule binding by the Ndc80 kinetochore complex.
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Nat Struct Mol Biol,
19,
1161-1167.
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E.Vladimirou,
E.Harry,
N.Burroughs,
and
A.D.McAinsh
(2011).
Springs, clutches and motors: driving forward kinetochore mechanism by modelling.
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Chromosome Res,
19,
409-421.
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H.Zhang,
and
R.K.Dawe
(2011).
Mechanisms of plant spindle formation.
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Chromosome Res,
19,
335-344.
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J.Tooley,
and
P.T.Stukenberg
(2011).
The Ndc80 complex: integrating the kinetochore's many movements.
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Chromosome Res,
19,
377-391.
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A.Petrovic,
S.Pasqualato,
P.Dube,
V.Krenn,
S.Santaguida,
D.Cittaro,
S.Monzani,
L.Massimiliano,
J.Keller,
A.Tarricone,
A.Maiolica,
H.Stark,
and
A.Musacchio
(2010).
The MIS12 complex is a protein interaction hub for outer kinetochore assembly.
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J Cell Biol,
190,
835-852.
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A.R.Cole,
L.P.Lewis,
and
H.Walden
(2010).
The structure of the catalytic subunit FANCL of the Fanconi anemia core complex.
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Nat Struct Mol Biol,
17,
294-298.
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PDB code:
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C.Rumpf,
L.Cipak,
A.Schleiffer,
A.Pidoux,
K.Mechtler,
I.M.Tolić-Nørrelykke,
and
J.Gregan
(2010).
Laser microsurgery provides evidence for merotelic kinetochore attachments in fission yeast cells lacking Pcs1 or Clr4.
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Cell Cycle,
9,
3997-4004.
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G.M.Alushin,
V.H.Ramey,
S.Pasqualato,
D.A.Ball,
N.Grigorieff,
A.Musacchio,
and
E.Nogales
(2010).
The Ndc80 kinetochore complex forms oligomeric arrays along microtubules.
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Nature,
467,
805-810.
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PDB code:
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K.D.Corbett,
C.K.Yip,
L.S.Ee,
T.Walz,
A.Amon,
and
S.C.Harrison
(2010).
The monopolin complex crosslinks kinetochore components to regulate chromosome-microtubule attachments.
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Cell,
142,
556-567.
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PDB codes:
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T.U.Tanaka
(2010).
Kinetochore-microtubule interactions: steps towards bi-orientation.
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EMBO J,
29,
4070-4082.
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A.F.Powers,
A.D.Franck,
D.R.Gestaut,
J.Cooper,
B.Gracyzk,
R.R.Wei,
L.Wordeman,
T.N.Davis,
and
C.L.Asbury
(2009).
The Ndc80 kinetochore complex forms load-bearing attachments to dynamic microtubule tips via biased diffusion.
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Cell,
136,
865-875.
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M.R.Przewloka,
and
D.M.Glover
(2009).
The kinetochore and the centromere: a working long distance relationship.
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Annu Rev Genet,
43,
439-465.
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R.B.Schittenhelm,
R.Chaleckis,
and
C.F.Lehner
(2009).
Intrakinetochore localization and essential functional domains of Drosophila Spc105.
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EMBO J,
28,
2374-2386.
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C.Ciferri,
S.Pasqualato,
E.Screpanti,
G.Varetti,
S.Santaguida,
G.Dos Reis,
A.Maiolica,
J.Polka,
J.G.De Luca,
P.De Wulf,
M.Salek,
J.Rappsilber,
C.A.Moores,
E.D.Salmon,
and
A.Musacchio
(2008).
Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex.
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Cell,
133,
427-439.
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PDB code:
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C.L.Asbury,
and
T.N.Davis
(2008).
Insights into the kinetochore.
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Structure,
16,
834-836.
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I.M.Cheeseman,
and
A.Desai
(2008).
Molecular architecture of the kinetochore-microtubule interface.
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Nat Rev Mol Cell Biol,
9,
33-46.
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T.U.Tanaka
(2008).
Bi-orienting chromosomes: acrobatics on the mitotic spindle.
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Chromosoma,
117,
521-533.
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T.U.Tanaka,
and
A.Desai
(2008).
Kinetochore-microtubule interactions: the means to the end.
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Curr Opin Cell Biol,
20,
53-63.
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R.B.Schittenhelm,
S.Heeger,
F.Althoff,
A.Walter,
S.Heidmann,
K.Mechtler,
and
C.F.Lehner
(2007).
Spatial organization of a ubiquitous eukaryotic kinetochore protein network in Drosophila chromosomes.
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Chromosoma,
116,
385-402.
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R.R.Wei,
J.Al-Bassam,
and
S.C.Harrison
(2007).
The Ndc80/HEC1 complex is a contact point for kinetochore-microtubule attachment.
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Nat Struct Mol Biol,
14,
54-59.
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PDB code:
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S.Westermann,
D.G.Drubin,
and
G.Barnes
(2007).
Structures and functions of yeast kinetochore complexes.
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Annu Rev Biochem,
76,
563-591.
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T.N.Davis,
and
L.Wordeman
(2007).
Rings, bracelets, sleeves, and chevrons: new structures of kinetochore proteins.
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Trends Cell Biol,
17,
377-382.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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}
}
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