Sun Chaohong, Nettesheim David, Liu Zhihong, Olejniczak Edward T
Global Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064-6098, USA.
Biochemistry. 2005 Jan 11;44(1):11-7. doi: 10.1021/bi0485171.
NMR studies of the antiapoptotic protein survivin have been used to determine the homodimer interface of the protein in solution and to identify residues of the protein that interact with Smac/Diablo. In solution, survivin(1-120) forms a bow-tie-shaped dimer whose interface is composed of its N-terminal residues as well as residues connecting its BIR domain to the C-terminal alpha helix. The solution structure resolves the controversy regarding the two possible dimer interfaces for survivin observed in X-ray crystal structures. The structural basis for the interaction between survivin and Smac/Diablo was also investigated. When Smac/Diablo or N-terminal Smac/Diablo peptide analogues are added to a solution of survivin, specific residues near alpha4 and beta3 are perturbed. NMR experiments indicate that the peptides bind across the third beta-strand of survivin in a manner similar to the way Smac/Diablo peptides bind to the BIR3 domain of X-linked IAP (XIAP).
抗凋亡蛋白survivin的核磁共振（NMR）研究已用于确定该蛋白在溶液中的同型二聚体界面，并识别与Smac/Diablo相互作用的蛋白残基。在溶液中，survivin(1-120)形成一个领结状二聚体，其界面由其N端残基以及连接其BIR结构域与C端α螺旋的残基组成。溶液结构解决了在X射线晶体结构中观察到的survivin两种可能二聚体界面的争议。还研究了survivin与Smac/Diablo相互作用的结构基础。当将Smac/Diablo或N端Smac/Diablo肽类似物添加到survivin溶液中时，α4和β3附近的特定残基会受到干扰。NMR实验表明，这些肽以类似于Smac/Diablo肽与X连锁凋亡抑制蛋白（XIAP）的BIR3结构域结合的方式，跨survivin的第三条β链结合。
