The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site
Jérémie Prévost, William D. Tolbert, Halima Medjahed, Rebekah Sherburn, Navid Madani, Daria Zoubchenok, Gabrielle Gendron‐Lepage, Althea Gaffney, Melissa C. Grenier‐Davies, Sharon Kirk, Natasha Gupta Vergara, Changze Han, Brendan T. Mann, Agnès L. Chénine, Adel A. Rashad, Irwin Chaiken, Frank Kirchhoff, Beatrice H. Hahn, Hillel Haim, Cameron F. Abrams, Amos B. Smith, Joseph Sodroski, Marzena Pazgier, Andrés Finzi
Abstract
The Phe43 cavity of HIV-1 envelope glycoproteins (Env) is an attractive druggable target. New promising compounds, including small CD4 mimetics (CD4mc), were shown to insert deeply into this cavity. Here, we identify a new network of residues that helps to shape this highly conserved CD4 binding pocket and characterize the structural determinants responsible for Env sensitivity to small CD4 mimetics.