Fig. 9: CryoET structure of HIV-1 Env in complex with CJF-III-288 and 17b Abs on virions. | Nature Communications

Fig. 9: CryoET structure of HIV-1 Env in complex with CJF-III-288 and 17b Abs on virions.

From: The asymmetric opening of HIV-1 Env by a potent CD4 mimetic enables anti-coreceptor binding site antibodies to mediate ADCC

Fig. 9

a AT-2 inactivated HIV-1BaL was incubated with 100 µM CJF-III-288 before addition of 100 µg/ml 17b Abs and subsequent plunge freezing for cryoET analysis. Tomographic slices of 17b Abs binding to Env on virions in the presence of CJF-III-288 are shown (blue: 17b, green: Env). Representative tomographic slices from three different tomograms collected from one sample preparation are shown. b Subtomogram averaging was performed on Env in complex with CJF-III-288 and 17b Abs (EMDB: 46646). A central slice along the density is shown. Panels to the right show three slices along the length of the structure. 17b Fabs and V1/V2 loops are indicated by arrows. c Isosurface rendering of the structure. d The atomic model of BG505 SOSIP.664 in complex with CJF-III-288 and 17b Fab (PDB:9CF5, this paper) was rigidly fit into the cryoET density. e The atomic model of BG505 SOSIP.664 in complex with BNM-III-170 and 17b Fab (PDB: 7LO6)44 was superimposed onto the gp41 helices of the CJF-III-288 atomic model. The three 17b Fab domains from the BNM-III-170 structure (blue) and the CJF-III-288 structure (red) are compared for their agreement with the cryoET density. The gp120 (green) and gp41 (gray) subunits from the CJF-III-288 structure and BNM-III-170 structure are shown in darker and lighter shades, respectively. f Focused classification revealed heterogeneity in the 17b fab position. Two representative subclasses are shown (pink and yellow) and compared to the combined average (gray). g The angle between the 17b Fabs from subclass 1 and subclass 2 relative to the approximate position of N335 (green sphere) is shown for each protomer. h Focused classification on the membrane region revealed subclasses at different tilting angles. Two representative subclasses (pink and yellow) are compared with the combined average density (gray). i Per-particle tilting analysis. The polar plot coloring indicates the normalized frequency of angles (n = 3512). j Histogram and box-and-whisker plot of the data in (i) showing the distribution of Env tilting (n = 3512). The median, range, and interquartile ranges (IQR) are shown. The mode is indicated by a red circle and a dashed line. Source data for i, j are provided as a Source Data file.

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