Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together.
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.
Jeyaprakash
A Arockia
AA
Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Klein
Ulf R
UR
Lindner
Doris
D
Ebert
Judith
J
Nigg
Erich A
EA
Conti
Elena
E
D000595:Amino Acid Sequence; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D002503:Centromere / Q000235:genetics / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D048749:Cytokinesis; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000502:physiology*; D000077022:Survivin
C107489:BIRC5 protein, human; C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases