Fig. 4: FP trajectory upon CD4-induced Env opening.
From: Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening
A HIV-1 Env structures organized by extent of opening. Left to right: closed, VRC34.01-bound Env (PDB: 5I8H) with gp41 colored olive, FPPR orange and FP cyan; partially open, CD4,17b,VRC34.01-bound Env (PDB:9D90; this study) with gp41 colored black, FPPR light green and FP cyan; partially open, CD4,17b,8ANC195-bound Env (PDB:6CM3) with gp41 colored magenta, FPPR light pink and FP teal; partially open CD4,17b,VRC34.01-bound Env (EMD-46671; this study) with gp41 colored black, FPPR light green and FP cyan; fully open, CD4,17b-bound Env (PDB:5VN3) with gp41 colored blue, FPPR light blue and FP cyan. The gp120 subunit is colored gray. Inset: Zoomed-in view of region around α0 helix (green). B 180° rotated views A with brown squares around the FP (colored cyan except in partially open CD,17b,8ANC195-bound BG505 structure, where it is colored teal). C Zoomed-in views of region around FP. Red arrows indicate direction of CD4-induced Env opening from pre-CD4, closed Env to CD4-induced fully open Env. D Comparisons of gp41 organization between fully open Env with sequestered and inaccessible FP (PDB: 5VN3), and (left) P1 (transiently exposed FP), (middle) partially open Env with transiently buried FP (PDB: 6CM3), and (right) P2 (inaccessible FP). Red arrows (left and middle panels) indicate HR2 movement that allows the FPPR to re-orient creating space for FP burial. E–G Locations in Env structure (PDB 4ZMJ fitted into EMDB-21412) where two fluorophores (Cy3 and Cy5 derivatives) are attached for smFRET imaging (E), three-dimensional presentation (F) and quantification (G) of conformational distribution-indicated FRET histograms observed from the gp120-gp41 perspective. The probability of each state (G), presented as mean ± s.e.m. (uncertainty), was derived from histograms (F), each compiled from Nm > 200 traces (specifically, 241, 213, 236, and 242), as detailed in Fig. S12F. The determining parameters are listed in Table S4. Virus EnvBG505 samples three primary conformational states (PT Pre-triggered, PC Prefusion Closed, and CO: CD4-bound open). PT predominates in the ligand-free condition, while VRC34 shifts the conformational landscape differently from that of the CD4-bound opening. Source data are provided as a Source Data file.
