Structure of a central component of the yeast kinetochore: the Spc24p/Spc25p globular domain.
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.
Wei
Ronnie R
RR
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Schnell
Jason R
JR
Larsen
Nicholas A
NA
Sorger
Peter K
PK
Chou
James J
JJ
Harrison
Stephen C
SC
D000595:Amino Acid Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D018386:Kinetochores / Q000737:chemistry; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*
D002868:Chromosomal Proteins, Non-Histone; D029701:Saccharomyces cerevisiae Proteins; C500717:Spc24 protein, S cerevisiae; C500718:Spc25 protein, S cerevisiae