VLDL-受体的配体结合结构域结构分析

The Structure Analysis of VLDL Receptor' s Ligand - binding Domain

极低密度脂蛋白受体(VLDL-R)的配体结合域具有8个富含半胱氨酸的配体结合重复序列(ligand-binding repeats,LBR),被认为是与配体结合的部位。该受体与含7个类似重复序列的低密度脂蛋白受体(LDL-R)的配体结合特性明显不同。为了明确VLDL-R中8个LBR在配体结合中的作用并探讨结合位点的结构,本研究采用计算机辅助蛋白质结构预测方法,在二级结构分析的基础上,通过同源建模方法预测受体N-端328个氨基酸的配体结合域空间结构,结果显示该区域呈现弧形口袋样结构,其中前3个LBR结构紧凑,呈棒状,负电荷相对集中,推测这一特征结构是配体结合的重要结构基础,结构分析同时表明在LBR5与LBR6之间连接区的弹性结构可以赋予结合位点一定的伸缩性,利于其与不同配体的结合。本研究预测结果首次提出了VLDL-R配体结构域结构及结合位点的结构特征,并与已有的实验结果一致。

The ligand - binding domain of the very low - density lipoprotein receptor( VLDL - R) contains eight cysteine - rich repeal sequences that have been postulated as place for ligand - binding. Its binding characterise is obviously different from that of low - density lipoprotein receptor( LDL - R) with seven similar repeats. To make clear the contribution of these repeats to ligand- binding and to explore the ligand- binding rites' structure, the method of protein structure prediction were adapted to analysize the 328 amino acids sequence of the receptor' N - end which showed an arc pocket - like structure, in this structure,there was a tightly clavate region clustered with negative charge formed by the front three LBRs, which was supposed to be the important structural base for binding with ligand.In addition, the joint sequence,between LBRS and LBR6, confer the davate structure some flexibility which will be helpful to binding with ligand.It was the first time to put forward the structure of VLDL - R ligand - binding domain and its combining - site that was consistent with the result from experiment studies.