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

Survivin is a 16.5 kDa protein that is expressed during the G2/M phase of t he cell cycle and is hypothesized to inhibit a default apoptotic cascade in itiated in mitosis. This inhibitory function is coupled to survivin's local ization to the mitotic spindle. To begin to address the structural basis of survivin's function, we report the X-ray crystal structure of a recombinan t form of full length survivin to 2.58 Angstrom resolution. Survivin consis ts of two defined domains including an N-terminal Zn2+-binding BIR domain l inked to a 65 Angstrom amphipathic C-terminal alpha-helix. The crystal stru cture reveals an extensive dimerization interface along a hydrophobic surfa ce on the BIR domain of each survivin monomer. A basic patch acting as a su lfate/phosphate-binding module, an acidic cluster projecting off the BIR do main, and a solvent-accessible hydrophobic surface residing on the C-termin al amphipathic helix, are suggestive of functional protein-protein interact ion surfaces.