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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

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:
 [1] ;  [2] ;  [2] ;  [2] ;  [2] ;  [2] ;  [1]
  1. New York Univ. School of Medicine, New York, NY (United States)
  2. Univ. of Massachusetts Medical School, Worcester, MA (United States)
Publication Date:
OSTI Identifier:
1214782
Grant/Contract Number:
AC02-06CH11357; AC02-98CH10886
Type:
Accepted Manuscript
Journal Name:
Emerging Microbes & Infections
Additional Journal Information:
Journal Volume: 4; Journal Issue: 7; Journal ID: ISSN 2222-1751
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States);Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES C4; CD4; Env; HIV-1; monoclonal antibody