2qfa

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Crystal structure of a Survivin-Borealin-INCENP core complexCrystal structure of a Survivin-Borealin-INCENP core complex

Structural highlights

2qfa is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Gene:BIRC5, API4, IAP4 (HUMAN), CDCA8, PESCRG3 (HUMAN), INCENP (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BIRC5_HUMAN] Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform.[1] [2] [3] [4] [5] [6] [7] [8] [INCE_HUMAN] Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Probably acts through association with AURKB or AURKC. Seems to bind directly to microtubules. Controls the kinetochore localization of BUB1.[9] [10] [11] [BOREA_HUMAN] Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. In the complex, it may be required to direct the CPC to centromeric DNA. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment.[12] [13] [14] [15]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together.,Jeyaprakash AA, Klein UR, Lindner D, Ebert J, Nigg EA, Conti E Cell. 2007 Oct 19;131(2):271-85. PMID:17956729[16]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Mahotka C, Wenzel M, Springer E, Gabbert HE, Gerharz CD. Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res. 1999 Dec 15;59(24):6097-102. PMID:10626797
  2. ↑ Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998 Dec 10;396(6711):580-4. PMID:9859993 doi:10.1038/25141
  3. ↑ Marusawa H, Matsuzawa S, Welsh K, Zou H, Armstrong R, Tamm I, Reed JC. HBXIP functions as a cofactor of survivin in apoptosis suppression. EMBO J. 2003 Jun 2;22(11):2729-40. PMID:12773388 doi:10.1093/emboj/cdg263
  4. ↑ Vong QP, Cao K, Li HY, Iglesias PA, Zheng Y. Chromosome alignment and segregation regulated by ubiquitination of survivin. Science. 2005 Dec 2;310(5753):1499-504. PMID:16322459 doi:10.1126/science.1120160
  5. ↑ Noton EA, Colnaghi R, Tate S, Starck C, Carvalho A, Ko Ferrigno P, Wheatley SP. Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis. J Biol Chem. 2006 Jan 13;281(2):1286-95. Epub 2005 Nov 16. PMID:16291752 doi:M508773200
  6. ↑ Xia F, Canovas PM, Guadagno TM, Altieri DC. A survivin-ran complex regulates spindle formation in tumor cells. Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. PMID:18591255 doi:10.1128/MCB.02039-07
  7. ↑ Wang H, Holloway MP, Ma L, Cooper ZA, Riolo M, Samkari A, Elenitoba-Johnson KS, Chin YE, Altura RA. Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity. J Biol Chem. 2010 Nov 12;285(46):36129-37. doi: 10.1074/jbc.M110.152777. Epub, 2010 Sep 8. PMID:20826784 doi:10.1074/jbc.M110.152777
  8. ↑ Pavlyukov MS, Antipova NV, Balashova MV, Vinogradova TV, Kopantzev EP, Shakhparonov MI. Survivin monomer plays an essential role in apoptosis regulation. J Biol Chem. 2011 Jul 1;286(26):23296-307. doi: 10.1074/jbc.M111.237586. Epub, 2011 May 2. PMID:21536684 doi:10.1074/jbc.M111.237586
  9. ↑ Li X, Sakashita G, Matsuzaki H, Sugimoto K, Kimura K, Hanaoka F, Taniguchi H, Furukawa K, Urano T. Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C. J Biol Chem. 2004 Nov 5;279(45):47201-11. Epub 2004 Aug 16. PMID:15316025 doi:http://dx.doi.org/10.1074/jbc.M403029200
  10. ↑ Honda R, Korner R, Nigg EA. Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol Biol Cell. 2003 Aug;14(8):3325-41. Epub 2003 May 29. PMID:12925766 doi:http://dx.doi.org/10.1091/mbc.E02-11-0769
  11. ↑ Qi W, Tang Z, Yu H. Phosphorylation- and polo-box-dependent binding of Plk1 to Bub1 is required for the kinetochore localization of Plk1. Mol Biol Cell. 2006 Aug;17(8):3705-16. Epub 2006 Jun 7. PMID:16760428 doi:http://dx.doi.org/10.1091/mbc.E06-03-0240
  12. ↑ Sampath SC, Ohi R, Leismann O, Salic A, Pozniakovski A, Funabiki H. The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. Cell. 2004 Jul 23;118(2):187-202. PMID:15260989 doi:http://dx.doi.org/10.1016/j.cell.2004.06.026
  13. ↑ Gassmann R, Carvalho A, Henzing AJ, Ruchaud S, Hudson DF, Honda R, Nigg EA, Gerloff DL, Earnshaw WC. Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. J Cell Biol. 2004 Jul 19;166(2):179-91. Epub 2004 Jul 12. PMID:15249581 doi:http://dx.doi.org/10.1083/jcb.200404001
  14. ↑ Klein UR, Nigg EA, Gruneberg U. Centromere targeting of the chromosomal passenger complex requires a ternary subcomplex of Borealin, Survivin, and the N-terminal domain of INCENP. Mol Biol Cell. 2006 Jun;17(6):2547-58. Epub 2006 Mar 29. PMID:16571674 doi:http://dx.doi.org/10.1091/mbc.E05-12-1133
  15. ↑ Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell. 2008 Jan 25;132(2):233-46. doi: 10.1016/j.cell.2007.11.046. PMID:18243099 doi:10.1016/j.cell.2007.11.046
  16. ↑ Jeyaprakash AA, Klein UR, Lindner D, Ebert J, Nigg EA, Conti E. Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. Cell. 2007 Oct 19;131(2):271-85. PMID:17956729 doi:http://dx.doi.org/10.1016/j.cell.2007.07.045

2qfa, resolution 1.40Å

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