Is it Ever Too Early?

IAVIReport, 16(3), 2012.



When the trimeric HIV Envelope (Env) spike binds its receptor on the target cell, it opens up and exposes an inner portion called gp41 that then drives fusion of the viral membrane with the target cell membrane. Recently, we determined the detailed three-dimensional shape of this open state of Env (PLoS Pathog. 8, e1002797, 2012). They rst showed that if they mixed an antibody called 17b with a water-soluble version of the Env trimer that only contained the parts outside the viral membrane and had a disul de bond between the gp41 and gp120 parts, they could stabilize Env in the open conformation. They then rapidly froze the complex of 17b and Env and determined its structure using cryo- electron microscopy. The image shows this structure of the opened Env trimer bound to 17b at 9 Å resolution (gray mesh), lled with the known X-ray structures of its components. The three exposed gp41 helices are in the center (protein backbone in red), surrounded by three copies of gp120 (N-terminal helix in yellow) bound to 17b (light chain: purple; heavy chain: blue).