4ZTP

Fab structure of rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region

Summary for 4ZTP

• Entry DOI: 10.2210/pdb4ztp/pdb
• Related: 4ZTO
• Descriptor: Light chain of Fab fragment of rabbit monoclonal antibody R53, Heavy chain of Fab fragment of rabbit monoclonal antibody R53 (3 entities in total)
• Functional Keywords: hiv-1, env, c4, cd4, monoclonal antibody, immune system
• Biological source: Oryctolagus cuniculus; More
• Total number of polymer chains: 2
• Total formula weight: 46344.64

Authors

Pan, R.,Kong, X.-P. (deposition date: 2015-05-14, release date: 2015-08-19, Last modification date: 2024-10-30)

Primary citation

Pan, R.,Chen, Y.,Vaine, M.,Hu, G.,Wang, S.,Lu, S.,Kong, X.P.
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.
Emerg Microbes Infect, 4:e44-e44, 2015

PubMed 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 (433)AMYAPPI(439), 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.

PubMed: 26251831
DOI: 10.1038/emi.2015.44

Experimental method

X-RAY DIFFRACTION (1.63 Å)