WMothes2/2 The difficulty working with intact viruses and receptor embedded in membranes is to get enough Env-CD4 complexes to allow subtomogram averaging. Importantly, sub classification clearly points to the existence of Env trimers that only bind 1 CD4 molecule when membranes are far apart. As HIV moves closer to the membrane, it binds 2 and then 3 receptor molecules. The conformation of Env is clearly asymmetric. These intermediates are likely important for antiviral therapies and immunogen design
I attach the main figure for our report. As HIV-1 approaches the cell host membrane, the envelope glycoprotein binds initially just 1 CD4 receptor molecule, then 2 and finally 3 CD4 receptor molecules as it moves closer to the cell membrane. Fascinating for us to see that asymmetric Env trimers bound to 1 and 2 CD4 receptor molecules are readily observed by cryo-electron tomography.