Myostatin三维结构模建及分子进化分析

Myostatin(MST)为肌肉生长负调节因子,其功能受抑制可导致肌肉量增加.对MST核酸序列进行序列比对,构建进化树;采用同源模建方法首次模建MST成熟肽生物活性二聚体的四级结构,并预测MST与其受体ActRIIB的相互作用模式.进化树将肌肉生长抑制素基因(MSTN)分成4个亚家族:哺乳动物MSTN,鸟类MSTN以及鱼类MSTN 1和2.MST受纯化选择作用,在不同物种的直系同源基因具有较高的刚源性,其中哺乳动物、鸟类MST C端活性肽氨基酸序列高度保守.表明哺乳动物、鸟类MST的结构、功能类似,且信号传导路径可能一致;而鱼类MST的调控机制可能存在较大差异.MST结构及其表面静电势和疏水氨基酸分布表明静电力和疏水相互作用在MST与其受体结合过程中可能起到十分重要的作用.

Homology Modeling and Molecular Evolution Analysis of Myostatin

Myostatin(MST) is the cytokine negatively regulated skeletal muscle growth factor, and the loss of function caused by mutations is associated with increased skeletal muscle mass.The multiple sequence alignment of the available MST cDNA sequences and the related evolutionary analyses were performed;the quarternary structures of MST homodimer and the MST:ActRIIB complex was built using homology modelling technique.The phylogenetic tree revealed that there were four sub-families, i.e., mammalian MSTN, avian MSTN, and fish MSTN1, 2 in the MST gene(MSTN) family.MST orthologous genes derived from different species had a high sequence identity, which were probably caused by the purifying selection.Particularly, the high degree of conservation of C-terminal sequences of mammalian and avian MST mature peptides suggested they shared the very similar structure, function and signal transduction pathway.The analyses of electrostatic potential and hydrophobic amino acid distribution of the structural models revealed that the electrostatic force and hydrophobic interaction played an important role in receptor recognition by MST.