Fig. 1. Cryo-EM structure of nanodisc-embedded HIV-1 gp145.

a Domain architecture of gp160. FP, fusion peptide; NHR, N-terminal heptad repeat; CHR, C-terminal heptad repeat (orange); MPER-N (green); MPER-C (magenta); TM, transmembrane domain; CT, cytoplasmic tail. Numbers above indicate the first residues of the segments and the numbers below the last. b Left: Cryo-EM map of nanodisc-embedded gp145 at a low contour level (0.011). The density for the nanodisc is shown in light yellow. Right: Cryo-EM map of nanodisc-embedded gp145 at a higher contour level (0.014) shown in semi-transparent gray, with the modeled gp145 structure, shown in ribbon representation, fit into the map. The CHR region is shown in orange and the MPER-N segment in green. The rest of the ectodomain is shown in blue. c Left: Structure of gp145 seen parallel (top) and perpendicular to the membrane plane (bottom). Right: Same views as in the left panel after adding the NMR structure of the complete MPER (PDB: 2PV6) to our gp145 model (based on an overlay of the MPER-N segments). The CHR region is shown in orange, the MPER-N segment in green, and the MPER-C segment in magenta. d Placement of the two available NMR structures of MPER-TM into the cryo-EM map (placed based on the position of the MPER-N segments). The tripod structure (PDB: 6DLN) fits well into the map (left), whereas the MPER-N segments of the stalk–bubble structure (PDB: 6E8W) correspond poorly with the cryo-EM map as the transmembrane helices protrude far from the nanodisc density (right). e Three cryo-EM maps of nanodisc-embedded gp145 showing that the gp145 ectodomain adopts a wide range of angles with respect to the membrane plane. The maps are shown as semi-transparent surfaces, and the structure of the ectodomain as colored ribbons. Distances were measured from the end of the ectodomain (residue Ala662) to the center of the nanodisc (indicated by the dashed line).