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Structure of Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition

43 Pages Posted: 5 Aug 2019 Sneak Peek Status: Under Review

See all articles by Jason Gorman

Jason Gorman

National Institutes of Health - Vaccine Research Center

Gwo-Yu Chuang

National Institutes of Health - Vaccine Research Center

Yen-Ting Lai

National Institutes of Health - Vaccine Research Center

Chen-Hsiang Shen

National Institutes of Health - Vaccine Research Center

Jeffrey C. Boyington

National Institutes of Health - Vaccine Research Center

Aliaksandr Druz

National Institutes of Health - Vaccine Research Center

Hui Geng

National Institutes of Health - Vaccine Research Center

Mark K. Louder

National Institutes of Health - Vaccine Research Center

Krisha McKee

Government of the United States of America - Vaccine Research Center

Reda Rawi

National Institutes of Health - Vaccine Research Center

Raffaello Verardi

National Institutes of Health - Vaccine Research Center

Yongping Yang

National Institutes of Health - Vaccine Research Center

Baoshan Zhang

National Institutes of Health - Vaccine Research Center

Nicole Doria-Rose

National Institutes of Health - Vaccine Research Center

Bob Lin

National Institutes of Health - Vaccine Research Center

Penny L. Moore

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Lynn Morris

University of the Witwatersrand

Lawrence Shapiro

National Institutes of Health - Vaccine Research Center

John R. Mascola

National Institutes of Health - Vaccine Research Center

Peter D. Kwong

National Institutes of Health - Vaccine Research Center

More...

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 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). Here we determine the cryo-electron microscopy structure at 3.8-Å resolution of the antigen-binding fragment of CAP256-VRC26.25 in complex with the Env trimer thought to have initiated the lineage. Remarkably, the 36-residue protruding loop of CAP256-VRC26.25 displayed 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.

Keywords: broadly neutralizing antibody, HIV-1 envelope trimer, multidonor antibody class, PCT64, PG9, PGDM1400, PGT145, tyrosine sulfation, V1V2-apex recognition

Suggested Citation

Gorman, Jason and Chuang, Gwo-Yu and Lai, Yen-Ting and Shen, Chen-Hsiang and Boyington, Jeffrey C. and Druz, Aliaksandr and Geng, Hui and Louder, Mark K. and McKee, Krisha and Rawi, Reda and Verardi, Raffaello and Yang, Yongping and Zhang, Baoshan and Doria-Rose, Nicole and Lin, Bob and Moore, Penny L. and Morris, Lynn and Shapiro, Lawrence and Mascola, John R. and Kwong, Peter D., Structure of Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition (August 5, 2019). CELL-REPORTS-D-19-03090. Available at SSRN: https://ssrn.com/abstract=3432644 or http://dx.doi.org/10.2139/ssrn.3432644
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Jason Gorman

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Gwo-Yu Chuang

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Yen-Ting Lai

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Chen-Hsiang Shen

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Jeffrey C. Boyington

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Aliaksandr Druz

National Institutes of Health - Vaccine Research Center

Bethesda, MD 20892-9806
United States

Hui Geng

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Mark K. Louder

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Krisha McKee

Government of the United States of America - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Reda Rawi

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Raffaello Verardi

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Yongping Yang

National Institutes of Health - Vaccine Research Center

Bethesda, MD 20892-9806
United States

Baoshan Zhang

National Institutes of Health - Vaccine Research Center

Bethesda, MD 20892-9806
United States

Nicole Doria-Rose

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Bob Lin

National Institutes of Health - Vaccine Research Center

Bethesda, MD 20892-9806
United States

Penny L. Moore

National Health Laboratory Services (NHLS) - Centre for HIV and STIs

Johannesburg
South Africa

Lynn Morris

University of the Witwatersrand

1 Jan Smuts Avenue
Johannesburg, 2000
South Africa

Lawrence Shapiro

National Institutes of Health - Vaccine Research Center

Bethesda, MD 20892-9806
United States

John R. Mascola

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Peter D. Kwong (Contact Author)

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

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