Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together

Cell. 2007 Oct 19;131(2):271-85. doi: 10.1016/j.cell.2007.07.045.

Abstract

The chromosomal passenger complex (CPC) is a key regulator of chromosome segregation and cytokinesis. CPC functions are connected to its localization. The complex first localizes to centromeres and later associates with the central spindle and midbody. Survivin, Borealin, and INCENP are the three components of the CPC that regulate the activity and localization of its enzymatic component, the kinase Aurora B. We determined the 1.4 A resolution crystal structure of the regulatory core of the CPC, revealing that Borealin and INCENP associate with the helical domain of Survivin to form a tight three-helical bundle. We used siRNA rescue experiments with structure-based mutants to explore the requirements for CPC localization. We show that the intertwined structural interactions of the core components lead to functional interdependence. Association of the core "passenger" proteins creates a single structural unit, whose composite molecular surface presents conserved residues essential for central spindle and midbody localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology
  • Centromere / genetics
  • Centromere / physiology
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / physiology
  • Chromosome Segregation / genetics
  • Chromosome Segregation / physiology*
  • Cytokinesis
  • Dimerization
  • HeLa Cells
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Protein Binding
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spindle Apparatus / genetics
  • Spindle Apparatus / physiology*
  • Survivin

Substances

  • BIRC5 protein, human
  • CDCA8 protein, human
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • INCENP protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Recombinant Proteins
  • Survivin
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases