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PreprintCited by 29Microtubule and mitosis dynamicsProtein Structure and DynamicsGenomics and Chromatin Dynamics

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Structures of the Ndc80 complex and its interactions at the yeast kinetochore-microtubule interface

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Zahm, Jacob, Jenni, Simon, Harrison, Stephen·2022·Open Biology
DOI 10.1101/2022.11.09.515846PMC PMC9993044

Preprint — published as 10.1098/rsob.220378

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Abstract

The conserved Ndc80 kinetochore complex, Ndc80c, is the principal link between spindle microtubules and centromere associated proteins during chromosome segregation. We used AlphaFold 2 to obtain structural predictions of the Ndc80 “loop” region and the Ndc80:Nuf2 globular head domains that interact with the Dam1 subunit of the decameric DASH/Dam1 complex (Dam1c). The predictions guided design of constructs that readily yielded crystal structures, essentially congruent with the predicted ones. The Ndc80 “loop” is a stiff, straight α-helical “switchback” structure, and flexibility within the long Ndc80c rod occurs instead at a hinge point between the globular head and the loop. Conserved stretches of the Dam1 C terminus bind Ndc80c with a short α helix followed by an extended segment such that phosphorylation of Dam1 serines 257, 265, and 292 by the mitotic kinase Ipl1/Aurora B can release this contact during error correction of mis-attached kinetochores. We integrate the structural results presented here into our current molecular model of the kinetochore-microtubule interface. The model illustrates how multiple interactions between Ndc80c, DASH/Dam1c and the microtubule lattice stabilize kinetochore attachments.

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  1. 10.1107/S0907444909052925 · DOI · Paper page
  2. 10.1107/S0907444912001308 · DOI · Paper page
  3. 10.1107/S1399004714028132 · DOI
  4. 10.1107/S2059798318006551 · DOI
  5. 10.1038/nature09423 · DOI
  6. 10.1093/nar/gks1195 · DOI · Paper page
  7. 10.1016/S0092-8674(02)00973-X · DOI
  8. 10.1107/S0907444909042073 · DOI · Paper page
  9. 10.1074/jbc.M504070200 · DOI
  10. 10.1016/j.cell.2008.03.020 · DOI
  11. 10.1016/j.cell.2016.10.011 · DOI
  12. 10.1107/S0907444910007493 · DOI · Paper page
  13. Flores, R.L. , Peterson, Z.E. , Zelter, A. , Riffle, M. , Asbury, C.L. , and Davis, T.N. (2022). Three interacting regions of the Ndc80 and Dam1 complexes support microtubule tip-coupling under load. J Cell Biol 221. · DOI
  14. 2022, xia2.multiplex: a multi-crystal data-analysis pipeline, Acta Crystallogr D Struct Biol, 78, 752, 10.1107/S2059798322004399 · DOI
  15. 10.1073/pnas.0807859105 · DOI
  16. 2020, Cdk1 Phosphorylation of the Dam1 Complex Strengthens Kinetochore-Microtubule Attachments, Curr Biol, 30, 4491, 10.1016/j.cub.2020.08.054 · DOI
  17. Herman, J.A. , Miller, M.P. , and Biggins, S. (2020). chTOG is a conserved mitotic error correction factor. Elife 9. · DOI
  18. 10.1038/nature03240 · DOI
  19. 10.1083/jcb.201612195 · DOI · Paper page
  20. 10.1016/j.cub.2010.12.048 · DOI
  21. 10.1371/journal.pone.0024109 · DOI
  22. Huis In ’t Veld, P.J. , Jeganathan, S. , Petrovic, A. , Singh, P. , John, J. , Krenn, V. , Weissmann, F. , Bange, T. , and Musacchio, A. (2016). Molecular basis of outer kinetochore assembly on CENP-T. Elife 5. · DOI
  23. Jenni, S. , Dimitrova, Y.N. , Valverde, R. , Hinshaw, S.M. , and Harrison, S.C. (2017). Molecular structures of yeast kinetochore subcomplexes and their roles in chromosome segregation. Cold Spring Harb Symp Quant Biol 82. · DOI
  24. 10.1126/science.aar6436 · DOI · Paper page
  25. 2017, The phosphorylation of a kinetochore protein Dam1 by Aurora B/Ipl1 kinase promotes chromosome bipolar attachment in yeast, Sci Rep, 7, 11880, 10.1038/s41598-017-12329-z · DOI
  26. 10.1107/S0108767390010224 · DOI
  27. 10.1002/bip.360221211 · DOI · Paper page
  28. 10.1093/nar/gkf436 · DOI · Paper page
  29. 10.1242/jcs.055566 · DOI
  30. Kiewisz, R. , Fabig, G. , Conway, W. , Baum, D. , Needleman, D. , and Muller-Reichert, T. (2022). Three-dimensional structure of kinetochore-fibers in human mitotic spindles. Elife 11. · DOI
  31. Kim, J.O. , Zelter, A. , Umbreit, N.T. , Bollozos, A. , Riffle, M. , Johnson, R. , MacCoss, M.J. , Asbury, C.L. , and Davis, T.N. (2017). The Ndc80 complex bridges two Dam1 complex rings. Elife 6. · DOI
  32. 10.1101/gad.449407 · DOI
  33. 2022, CCP4 Cloud for structure determination and project management in macromolecular crystallography, Acta Crystallogr D Struct Biol, 78, 1079, 10.1107/S2059798322007987 · DOI
  34. 10.1083/jcb.201210091 · DOI
  35. Legal, T. , Zou, J. , Sochaj, A. , Rappsilber, J. , and Welburn, J.P. (2016). Molecular architecture of the Dam1 complex-microtubule interaction. Open Biol 6. · DOI
  36. 2003, The DASH complex component Ask1 is a cell cycle-regulated Cdk substrate in Saccharomyces cerevisiae, Cell Cycle, 2, 143
  37. 10.1074/mcp.M700274-MCP200 · DOI
  38. 10.1038/emboj.2012.356 · DOI
  39. 10.1016/j.cub.2010.12.050 · DOI
  40. 10.1107/S0021889807021206 · DOI · Paper page
  41. 10.1083/jcb.201209154 · DOI
  42. 10.1016/j.cell.2016.04.030 · DOI
  43. 10.1371/journal.pgen.1008423 · DOI
  44. 10.1038/nsmb896 · DOI
  45. 10.1091/mbc.E07-02-0135 · DOI
  46. 10.1038/emboj.2012.348 · DOI
  47. 10.1006/jmbi.2000.4042 · DOI
  48. 10.1091/mbc.E19-07-0405 · DOI
  49. 10.1107/S0907444906005270 · DOI
  50. Polley, S. , Müschenborn, H. , Terbeck, M. , De Antoni, A. , Vetter, I.R. , Dogterom, M. , Musacchio, A. , Volkov, V.A. , and Huis In ’t Veld, P.J. (2022). Stable kinetochore-microtubule attachment requires loop-dependent Ndc80-Ndc80 binding. bioRxiv 2022.08.25.505310. · DOI · Paper page
  51. 10.1091/mbc.E10-10-0841 · DOI
  52. 10.1093/nar/gku316 · DOI · Paper page
  53. 10.1006/jsbi.2001.4336 · DOI
  54. 10.1016/j.cub.2006.06.063 · DOI
  55. 10.1016/j.cub.2013.06.040 · DOI
  56. 10.1093/nar/gki458 · DOI
  57. 10.1038/ncomms9161 · DOI
  58. 10.1083/jcb.200702141 · DOI
  59. 10.1038/nature03483 · DOI · Paper page
  60. 10.1091/mbc.E12-11-0817 · DOI
  61. 10.1107/S0907444900005072 · DOI
  62. Tickle, I.J. , Flensburg, C. , Keller, P. , Paciorek, W. , Sharff, A. , Vonrhein, C. , and Bricogne, G. (2018). STARANISO (http://staraniso.globalphasing.org/cgi-bin/staraniso.cgi) (Cambridge, United Kingdom: Global Phasing Ltd.).
  63. 10.1038/ncomms5951 · DOI
  64. 10.1093/nar/gkaa1100 · DOI · Paper page
  65. 2016, Conserved Tetramer Junction in the Kinetochore Ndc80 Complex, Cell Rep, 17, 1915, 10.1016/j.celrep.2016.10.065 · DOI
  66. 10.1093/gbe/evx088 · DOI
  67. 10.1016/j.jmb.2015.09.014 · DOI · Paper page
  68. 10.1016/j.jmb.2008.08.077 · DOI
  69. 10.1091/mbc.E12-05-0396 · DOI
  70. 10.1038/nsmb1186 · DOI
  71. 10.1016/j.str.2006.04.007 · DOI
  72. 10.1073/pnas.0501168102 · DOI
  73. 10.1016/j.molcel.2004.12.019 · DOI
  74. 10.1107/S0907444910045749 · DOI · Paper page
  75. 10.1002/pro.4224 · DOI
  76. Zahm, J.A. , Stewart, M.G. , Carrier, J.S. , Harrison, S.C. , and Miller, M.P. (2021). Structural basis of Stu2 recruitment to yeast kinetochores. Elife 10. · DOI

Metadata

Authors
Zahm, J., Jenni, S., & Harrison, S.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Harrison, Stephen
ORCID
Venue
Open Biology
Publisher
openRxiv
Published
2022-11-09
Volume
13
Issue
3
Pages
220378-220378
ISSN
2046-2441 (ISSN-L)
DOI
10.1101/2022.11.09.515846
PMC
PMC9993044
OpenAlex
W4323533512
Cited by
29
References
1
Citations by year
2026: 6 · 2025: 6 · 2024: 9 · 2023: 8
FWCI
4.20
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Open Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Howard Hughes Medical Institute
  • U.S. Department of Energy (DE‐ AC02‐06CH11357)
  • American Cancer Society (PF-21-188-01-CCB)
  • National Institutes of Health (DE-AC02–06CH11357, GM124165)
  • National Institute of General Medical Sciences (P30GM124165)
  • Argonne National Laboratory (DE- AC02-06-CH11357, DE-AC02, AC02–06CH11357, Contract DE-AC02-06CH11357, 06CH11357, P30 GM124165)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
Ndc80 complex, kinetochore-microtubule interface, Dam1 complex, NUF2, centromere, mitotic spindle, kinetochore attachment, Ipl1, Saccharomyces cerevisiae, protein structure prediction, AlphaFold2
MeSH terms
Centromere, Furylfuramide, Microtubule-Associated Proteins, Microtubules, Nuclear Proteins, Saccharomyces cerevisiae, Kinetochores, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, Aurora Kinase B, Aurora Kinases

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