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Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement

Nature Structural Biology volume 7, pages 602–608 (2000)Cite this article

Abstract

Survivin is a 16.5 kDa protein that is expressed during the G2/M phase of the cell cycle and is hypothesized to inhibit a default apoptotic cascade initiated in mitosis. This inhibitory function is coupled to survivin's localization to the mitotic spindle. To begin to address the structural basis of survivin's function, we report the X-ray crystal structure of a recombinant form of full length survivin to 2.58 Å resolution. Survivin consists of two defined domains including an N-terminal Zn2+-binding BIR domain linked to a 65 Å amphipathic C-terminal α-helix. The crystal structure reveals an extensive dimerization interface along a hydrophobic surface on the BIR domain of each survivin monomer. A basic patch acting as a sulfate/phosphate-binding module, an acidic cluster projecting off the BIR domain, and a solvent-accessible hydrophobic surface residing on the C-terminal amphipathic helix, are suggestive of functional protein–protein interaction surfaces.

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Figure 1: Structural features of human survivin.
Figure 2: Overall architecture of human survivin.
Figure 3: Surface features of human survivin.
Figure 4: Dimerization interfaces.
Figure 5: Sequence alignment of eight representative BIR domain containing proteins.
Figure 6: Hydrodynamic characterization of survivin.

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Acknowledgements

We thank J. Greenwald for assistance performing light scattering experiments. We also thank W. Jiang for providing a HeLa cell cDNA library. The SSRL Biotechnology Program is supported by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program, and by the Department of Energy, Office of Biological and Environmental Research. This work was supported by USPHS grants awarded to J.P.N. and T.H. T.H. is a Frank and Else Schilling American Cancer Society Professor. H.-k.H. is supported by a fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation.

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Authors and Affiliations

  1. Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, 92037 , California, USA

    Mark A. Verdecia, Erica Dutil, Donald A. Kaiser & Joseph P. Noel

  2. Department of Biology, University of California, San Diego, La Jolla, 92093, California, USA

    Mark A. Verdecia

  3. Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, 92037, California, USA

    Han-kuei Huang & Tony Hunter

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Correspondence to Joseph P. Noel.

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Verdecia, M., Huang, Hk., Dutil, E. et al. Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nat Struct Mol Biol 7, 602–608 (2000). https://doi.org/10.1038/76838

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