The pseudo GTPase CENP-M drives human kinetochore assembly

Federica Basilico, Stefano Maffini, John R. Weir, Daniel Prumbaum, Ana M. Rojas, Tomasz Zimniak, Anna De Antoni, Sadasivam Jeganathan, Beate Voss, Suzan Van Gerwen, Veronica Krenn, Lucia Massimiliano, Alfonso Valencia, Ingrid R. Vetter, Franz Herzog, Stefan Raunser, Sebastiano Pasqualato, Andrea Musacchio

Research output: Contribution to journalArticle

Abstract

Kinetochores, multi-subunit complexes that assemble at the interface with centromeres, bind spindle microtubules to ensure faithful delivery of chromosomes during cell division. The configuration and function of the kinetochore-centromere interface is poorly understood. We report that a protein at this interface, CENP-M, is structurally and evolutionarily related to small GTPases but is incapable of GTP-binding and conformational switching. We show that CENP-M is crucially required for the assembly and stability of a tetramer also comprising CENP-I, CENP-H, and CENP-K, the HIKM complex, which we extensively characterize through a combination of structural, biochemical, and cell biological approaches. A point mutant affecting the CENP-M/CENP-I interaction hampers kinetochore assembly and chromosome alignment and prevents kinetochore recruitment of the CENP-T/W complex, questioning a role of CENP-T/W as founder of an independent axis of kinetochore assembly. Our studies identify a single pathway having CENP-C as founder, and CENP-H/I/K/M and CENP-T/W as CENP-C-dependent followers.

Original languageEnglish
Article numbere02978
JournaleLife
Volume2014
Issue number3
DOIs
Publication statusPublished - Jul 8 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

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    Basilico, F., Maffini, S., Weir, J. R., Prumbaum, D., Rojas, A. M., Zimniak, T., De Antoni, A., Jeganathan, S., Voss, B., Van Gerwen, S., Krenn, V., Massimiliano, L., Valencia, A., Vetter, I. R., Herzog, F., Raunser, S., Pasqualato, S., & Musacchio, A. (2014). The pseudo GTPase CENP-M drives human kinetochore assembly. eLife, 2014(3), [e02978]. https://doi.org/10.7554/eLife.02978.001