Verdecia M A, Huang H, Dutil E, Kaiser D A, Hunter T, Noel J P
Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nat Struct Biol. 2000 Jul;7(7):602-8. doi: 10.1038/76838.
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 A resolution. Survivin consists of two defined domains including an N-terminal Zn2+-binding BIR domain linked to a 65 A amphipathic C-terminal alpha-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.
存活素是一种16.5 kDa的蛋白质，在细胞周期的G2/M期表达，据推测它能抑制有丝分裂中启动的默认凋亡级联反应。这种抑制功能与存活素定位于有丝分裂纺锤体有关。为了开始探讨存活素功能的结构基础，我们报道了全长重组存活素的X射线晶体结构，分辨率为2.58 Å。存活素由两个明确的结构域组成，包括一个与65 Å两亲性C端α螺旋相连的N端锌离子结合BIR结构域。晶体结构揭示了每个存活素单体BIR结构域上沿疏水表面的广泛二聚化界面。一个作为硫酸盐/磷酸盐结合模块的碱性斑块、一个从BIR结构域突出的酸性簇以及位于C端两亲性螺旋上的溶剂可及疏水表面，提示了功能性蛋白质-蛋白质相互作用表面。
