Binding of gp120 of ENV oligomer to the host CD4

CD4, located on the host cell membrane, is the main cellular receptor for the HIV protein gp120, which aids in mediating viral entry into target cells. The initial step in this cascade of events is the binding of viral gp120 protein to its host receptor, CD4. The key binding sites in CD4 for interaction with gp120 are located in the amino-terminal part of the CD4 molecule, distal to the transmembrane domain. The gp120 protein forms an oligomer (trimer) on the viral membrane with each gp120 protein containing variable domains (known as loops) and conservative domains. The V3 loop is also often obscured by gp120 glycosylation. Crystallization studies of CD4 suggest that the molecule has two immunoglobulin like domains important for the CD4/gp120 interaction, with one of the domains (D1) playing a more prominent role. Further studies suggest the Phe 43 and Arg 59 residues of CD4 play a major role in complex formation. Crystallization of gp120 shows that the polypeptide chain is folded into two major domains (an "inner" and "outer" domain with respect to the N and C termini), with the distal end of the “outer” domain containing the V3 loop. Studies of CD4 complexed with gp120 show that CD4 is bound to gp120 in a depression which is formed at the interface between the inner and outer domains. The complex itself is held together through van der Waals forces and hydrogen bonding.

CD4，位于宿主细胞膜上，是HIV蛋白gp120的主要细胞受体，有助于介导病毒进入靶细胞。此事件链的初始步骤是病毒gp120蛋白与其宿主受体CD4的结合。CD4与gp120相互作用的关键结合位点位于CD4分子的氨基末端部分，远离跨膜结构域。gp120蛋白在病毒膜上形成寡聚体（三聚体），其中每个gp120蛋白包含可变结构域（称为环）和保守结构域。V3环也常被gp120糖基化所掩盖。CD4的结晶学研究表明，该分子具有两个与CD4/gp120相互作用重要的免疫球蛋白样结构域，其中之一的结构域（D1）发挥着更为显著的作用。进一步的研究表明，CD4中的Phe 43和Arg 59残基在复合物形成中起着至关重要的作用。gp120的结晶化显示，多肽链折叠成两个主要结构域（相对于N端和C端，分别为“内部”和“外部”结构域），其中“外部”结构域的远端包含V3环。CD4与gp120的复合物研究表明，CD4结合在由内部和外部结构域界面形成的凹陷中。该复合物本身通过范德华力和氢键相互作用而保持稳定。