SAXS data analysis and modeling of tetravalent neutralizing antibody CD4-IgG2 -/+ HIV-1 gp120 revealed that first two gp120 bind to the same Fab arm.

This communication describes SAXS data based global structures of tetravalent antibody CD4-IgG2 and its dimeric to pentameric complexes with gp120s. Comparison of models brought forth that while the two CD4s grafted on each arm remain tightly packed in the unliganded antibody, they enable binding of first two gp120s preferentially to the same Fab arm in an asymmetric manner. Retention of residues in the CD4-Fab linker earlier reasoned to enable bi-fold collapse of gp120-bound soluble CD4, and observed asymmetry of the (CD4-IgG2)/(gp120)(2) complex suggest that encoded flexibility in CD4-Fab linker is a critical structure-function factor for this broad spectrum neutralizing antibody.