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The pseudo GTPase CENP-M drives human kinetochore assembly

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  • Additional Information
    • Contributors:
      Basilico, F; Maffini, S; Weir, J; Prumbaum, D; Rojas, A; Zimniak, T; De Antoni, A; Jeganathan, S; Voss, B; van Gerwen, S; Krenn, V; Massimiliano, L; Valencia, A; Vetter, I; Herzog, F; Raunser, S; Pasqualato, S; Musacchio, A
    • Publication Information:
      eLife Sciences Publications Ltd.
      GB
    • Publication Date:
      2014
    • Collection:
      Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive)
    • 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.
    • File Description:
      ELETTRONICO
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/25006165; info:eu-repo/semantics/altIdentifier/wos/WOS:000338742900002; volume:2014; issue:3; firstpage:1; lastpage:28; numberofpages:28; journal:ELIFE; https://hdl.handle.net/10281/397677; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84904052265
    • Accession Number:
      10.7554/eLife.02978
    • Online Access:
      https://hdl.handle.net/10281/397677
      https://doi.org/10.7554/eLife.02978
    • Rights:
      info:eu-repo/semantics/openAccess
    • Accession Number:
      edsbas.8B21C54F