National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM103310
United States
Citation
Journal: Cell Rep / Year: 2020 Title: Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition. Authors: Jason Gorman / Gwo-Yu Chuang / Yen-Ting Lai / Chen-Hsiang Shen / Jeffrey C Boyington / Aliaksandr Druz / Hui Geng / Mark K Louder / Krisha McKee / Reda Rawi / Raffaello Verardi / Yongping ...Authors: Jason Gorman / Gwo-Yu Chuang / Yen-Ting Lai / Chen-Hsiang Shen / Jeffrey C Boyington / Aliaksandr Druz / Hui Geng / Mark K Louder / Krisha McKee / Reda Rawi / Raffaello Verardi / Yongping Yang / Baoshan Zhang / Nicole A Doria-Rose / Bob Lin / Penny L Moore / Lynn Morris / Lawrence Shapiro / John R Mascola / Peter D Kwong / Abstract: Antibodies targeting the V1V2 apex of the HIV-1 envelope (Env) trimer comprise one of the most commonly elicited categories of broadly neutralizing antibodies. Structures of these antibodies indicate ...Antibodies targeting the V1V2 apex of the HIV-1 envelope (Env) trimer comprise one of the most commonly elicited categories of broadly neutralizing antibodies. Structures of these antibodies indicate diverse modes of Env recognition typified by antibodies of the PG9 class and the PGT145 class. The mode of recognition, however, has been unclear for the most potent of the V1V2 apex-targeting antibodies, CAP256-VRC26.25 (named for donor-lineage.clone and referred to hereafter as VRC26.25). Here, we determine the cryoelectron microscopy structure at 3.7 Å resolution of the antigen-binding fragment of VRC26.25 in complex with the Env trimer thought to have initiated the lineage. The 36-residue protruding loop of VRC26.25 displays recognition incorporating both strand-C interactions similar to the PG9 class and V1V2 apex insertion similar to the PGT145 class. Structural elements of separate antibody classes can thus intermingle to form a "combined" class, which in this case yields an antibody of extraordinary potency.
History
Deposition
Feb 10, 2020
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Header (metadata) release
Mar 11, 2020
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Map release
Mar 11, 2020
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Update
Oct 6, 2021
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Current status
Oct 6, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Model: C-flat-1.2/1.3 4C / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY
Vitrification
Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV
Details
CAP256 SU.wk34.80 SOSIP.RnS2
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 1760 / Average exposure time: 10.0 sec. / Average electron dose: 74.41 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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