Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding
Abstract
The fourth conserved region (C4) in the HIV-1 envelope glycoprotein (Env) gp120 is a structural element that is important for its function, as it binds to both the receptor CD4 and the co-receptor CCR5/CXCR4. It has long been known that this region is highly immunogenic and that it harbors B-cell as well as T-cell epitopes. It is the target of a number of antibodies in animal studies, which are called CD4-blockers. However, the mechanism by which the virus shields itself from such antibody responses is not known. Here, we determined the crystal structure of R53 in complex with its epitope peptide using a novel anti-C4 rabbit monoclonal antibody R53. Our data show that although the epitope of R53 covers a highly conserved sequence 433AMYAPPI439, it is not available in the gp120 trimer and in the CD4-bound conformation. Our results suggest a masking mechanism to explain how HIV-1 protects this critical region from the human immune system.
- Authors:
-
- New York Univ. School of Medicine, New York, NY (United States)
- Univ. of Massachusetts Medical School, Worcester, MA (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States); Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1214782
- Grant/Contract Number:
- AC02-06CH11357; AC02-98CH10886
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Emerging Microbes & Infections
- Additional Journal Information:
- Journal Volume: 4; Journal Issue: 7; Journal ID: ISSN 2222-1751
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; C4; CD4; Env; HIV-1; monoclonal antibody
Citation Formats
Pan, Ruimin, Chen, Yuxin, Vaine, Michael, Hu, Guangnan, Wang, Shixia, Lu, Shan, and Kong, Xiang -Peng. Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding. United States: N. p., 2015.
Web. doi:10.1038/emi.2015.44.
Pan, Ruimin, Chen, Yuxin, Vaine, Michael, Hu, Guangnan, Wang, Shixia, Lu, Shan, & Kong, Xiang -Peng. Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding. United States. https://doi.org/10.1038/emi.2015.44
Pan, Ruimin, Chen, Yuxin, Vaine, Michael, Hu, Guangnan, Wang, Shixia, Lu, Shan, and Kong, Xiang -Peng. Wed .
"Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding". United States. https://doi.org/10.1038/emi.2015.44. https://www.osti.gov/servlets/purl/1214782.
@article{osti_1214782,
title = {Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding},
author = {Pan, Ruimin and Chen, Yuxin and Vaine, Michael and Hu, Guangnan and Wang, Shixia and Lu, Shan and Kong, Xiang -Peng},
abstractNote = {The fourth conserved region (C4) in the HIV-1 envelope glycoprotein (Env) gp120 is a structural element that is important for its function, as it binds to both the receptor CD4 and the co-receptor CCR5/CXCR4. It has long been known that this region is highly immunogenic and that it harbors B-cell as well as T-cell epitopes. It is the target of a number of antibodies in animal studies, which are called CD4-blockers. However, the mechanism by which the virus shields itself from such antibody responses is not known. Here, we determined the crystal structure of R53 in complex with its epitope peptide using a novel anti-C4 rabbit monoclonal antibody R53. Our data show that although the epitope of R53 covers a highly conserved sequence 433AMYAPPI439, it is not available in the gp120 trimer and in the CD4-bound conformation. Our results suggest a masking mechanism to explain how HIV-1 protects this critical region from the human immune system.},
doi = {10.1038/emi.2015.44},
journal = {Emerging Microbes & Infections},
number = 7,
volume = 4,
place = {United States},
year = {Wed Jul 15 00:00:00 EDT 2015},
month = {Wed Jul 15 00:00:00 EDT 2015}
}
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