Moore J P, Jameson B A, Sattentau Q J, Willey R, Sodroski J
Aaron Diamond AIDS Research Center, New York University School of Medicine, New York 10016.
Philos Trans R Soc Lond B Biol Sci. 1993 Oct 29;342(1299):83-8. doi: 10.1098/rstb.1993.0139.
The HIV-1 surface glycoprotein gp120 binds CD4 in the initial state of virus-cell fusion. The extensive glycosylation of gp120 has thus far precluded definition of its structure by crystallographic methods. As an initial approach to a gp120 structure, the surface topology was mapped using antibodies. First, the regions of gp120 that are accessible on the surface of the native molecule, and those that are internal but exposed after denaturation, are identified. Second, epitopes for antibodies that recognize complex surface structures comprising segments of different domains are identified. Third, we define how mutations in one domain of gp120 influence the binding of antibodies to defined epitopes on other domains. These latter approaches enable us to start to understand the inter-domain interactions that contribute to the overall structure of the gp120 molecule. Information from these studies is being used to model the structures of individual gp120 domains, and the way in which these interact in the folded protein.
在病毒与细胞融合的初始阶段，HIV-1表面糖蛋白gp120与CD4结合。迄今为止，gp120广泛的糖基化作用使得通过晶体学方法确定其结构变得困难。作为研究gp120结构的初步方法，利用抗体绘制了其表面拓扑结构。首先，确定天然分子表面可及的gp120区域，以及那些位于内部但在变性后暴露的区域。其次，确定识别由不同结构域片段组成的复杂表面结构的抗体的表位。第三，我们确定gp120一个结构域中的突变如何影响抗体与其他结构域上特定表位的结合。后一种方法使我们能够开始理解有助于gp120分子整体结构的结构域间相互作用。这些研究所得信息正用于构建各个gp120结构域的模型，以及这些结构域在折叠蛋白中相互作用的方式。
