Architecture and flexibility of the yeast Ndc80 kinetochore complex.
Kinetochores mediate microtubule-chromosome attachment and ensure accurate segregation of sister chromatids. The highly conserved Ndc80 kinetochore complex makes direct contacts with the microtubule and is essential for spindle checkpoint signaling. It contains a long coiled-coil region with globular domains at each end involved in kinetochore localization and microtubule binding, respectively. We have directly visualized the architecture of the yeast Ndc80 complex and found a dramatic kink within the 560-A coiled-coil rod located about 160 A from the larger globular head. Comparison of our electron microscopy images to the structure of the human Ndc80 complex allowed us to position the kink proximal to the microtubule-binding end and to define the conformational range of the complex. The position of the kink coincides with a coiled-coil breaking region conserved across eukaryotes. We hypothesize that the kink in Ndc80 is essential for correct kinetochore geometry and could be part of a tension-sensing mechanism at the kinetochore.
Wang
Hong-Wei
HW
Life Science Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.
Long
Sydney
S
Ciferri
Claudio
C
Westermann
Stefan
S
Drubin
David
D
Barnes
Georjana
G
Nogales
Eva
E
D000595:Amino Acid Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008854:Microscopy, Electron; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D016415:Sequence Alignment; D013314:Stress, Mechanical
D002868:Chromosomal Proteins, Non-Histone; D046911:Macromolecular Substances; C112472:NDC80 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C500717:Spc24 protein, S cerevisiae; C500718:Spc25 protein, S cerevisiae
Cell. 2003 Feb 21;112(4):407-21
12600307
J Cell Sci. 2004 Nov 1;117(Pt 23):5461-77
15509863
J Struct Biol. 1999 Dec 1;128(1):82-97
10600563
Annu Rev Cell Dev Biol. 2003;19:519-39
14570580
Genome Biol. 2006;7(3):R23
16563186
Nat Rev Mol Cell Biol. 2008 Jan;9(1):33-46
18097444
Nat Cell Biol. 2006 Jun;8(6):581-5
16715078
Cell. 2006 Dec 1;127(5):983-97
17129783
FEBS Lett. 2007 Jun 19;581(15):2862-9
17521635
Curr Opin Cell Biol. 2008 Feb;20(1):53-63
18182282
J Struct Biol. 1996 Jan-Feb;116(1):17-24
8742718
J Biol Chem. 2005 Aug 12;280(32):29088-95
15961401
Cell. 2008 May 2;133(3):427-39
18455984
Mol Cell Proteomics. 2007 Dec;6(12):2200-11
17921176
J Cell Biol. 2004 Feb 16;164(4):535-46
14769859
Annu Rev Biochem. 2007;76:563-91
17362199
Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5363-7
15809444
J Cell Biol. 2008 May 19;181(4):587-94
18474626
J Cell Biol. 2003 Oct 27;163(2):215-22
14581449
Cell. 2006 Dec 1;127(5):969-82
17129782
Nat Struct Mol Biol. 2007 Jan;14(1):54-9
17195848
Curr Biol. 2008 Jan 22;18(2):81-90
18211850
Structure. 2006 Jun;14(6):1003-9
16765893
Mol Biol Cell. 2005 Feb;16(2):519-31
15548592
Nat Rev Mol Cell Biol. 2007 May;8(5):379-93
17426725