Unveiling the Dynamic Interactions of HIV-1 Env Trimers with CD4 Receptors

Researchers have used cryo-electron tomography to directly visualize the interactions between HIV-1 Env trimers and CD4 receptors in native membranes. They observed that Env-CD4 complexes cluster and organize into rings, with the patterns of clustering correlating with decreasing distances between membranes at the interfaces. Subtomogram averaging and classification revealed that as the membranes approached each other, Env trimers bound to two or three CD4 molecules. The V1V2 loop projected outward in the CD4-bound protomers, while the unbound protomers showed heterogeneous conformational states. These findings suggest that asymmetric HIV-1 Env trimers with one and two bound CD4 molecules are detectable intermediates during virus binding to membranes.