Fig. 1: Time-dependent conformational changes in HIV-1 BG505 SOSIP Env upon incubation with CD4.
From: Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening
A Structure of pre-fusion, pre-receptor, closed HIV-1 Env (PDB: 5I8H) bound to broadly neutralizing, fusion peptide-directed antibody VRC34.01. The Env is shown in surface representation with the gp120 subunits colored light gray, and within the gp120 subunits, the V1V2 loop colored wheat, V3 loop olive and the residues contributing to the bridging sheet in the open Env colored red. The gp41 subunits are colored black with the fusion peptide (FP) colored cyan. The antibody VRC34.01 is shown in ribbon representation bound to its FP-centered epitope. B Structure of pre-fusion, CD4-bound open HIV-1 Env bound to CD4-induced antibody 17b. The Env is colored similarly as in panel A. CD4 is shown as a yellow ribbon and 17b Fab is shown as an orange ribbon. C Surface plasmon based binding (SPR) analysis monitoring FP burial. Env was incubated at 25 °C with either sCD4 alone or with CD4 and the coreceptor mimicking antibody 17b. At different time-points after incubation, binding was measured to the fusion peptide targeting antibody VRC34.01. Some elements of the SPR schematic were created in BioRender. Acharya, P. (2025) https://BioRender.com/m74zcsz. D Simultaneous Env opening and fusion peptide burial were measured by incubating Env with CD4 and at different time-points injecting over a VRC34.01 IgG or a 17b IgG surface. Source data for panels (C, D) are provided as a Source Data file. Data shown are representative of at least two independent experiments. E Cryo-EM reconstructions of three distinct populations of CD4/17b-bound, partially open Env bound to VRC34.01. Population 1 is bound to VRC34.01 at all three sites. The blue arrows indicate sites unoccupied by VRC34.01 in Populations 2 and 3.
