4YBL

Crystal structure of the stabilized inner domain of clade A/E HIV-1 gp120 in complex with the ADCC mediating ANTI-HIV-1 antibody A32

Summary for 4YBL

• Entry DOI: 10.2210/pdb4ybl/pdb
• Related: 3TNM 4H8W 4RQH 4YC2
• Descriptor: Stabilized inner domain of clade A/E gp120, A32 antibody Fab heavy chain, A32 antibody light chain (3 entities in total)
• Functional Keywords: adcc, non-neutralizing, anti-hiv-1 env antibody a32, cd4i antibody, viral glycoprotein gp120, hiv-1 env, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 126843.38

Authors

Tolbert, W.D.,Gohain, N.,Pazgier, M. (deposition date: 2015-02-18, release date: 2016-03-02, Last modification date: 2024-10-30)

Primary citation

Tolbert, W.D.,Gohain, N.,Veillette, M.,Chapleau, J.P.,Orlandi, C.,Visciano, M.L.,Ebadi, M.,DeVico, A.L.,Fouts, T.R.,Finzi, A.,Lewis, G.K.,Pazgier, M.
Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region.
Structure, 24:697-709, 2016

PubMed Abstract: Evidence supports a role of antibody-dependent cellular cytotoxicity (ADCC) toward transitional epitopes in the first and second constant (C1-C2) regions of gp120 (A32-like epitopes) in preventing HIV-1 infection and in vaccine-induced protection. Here, we describe the first successful attempt at isolating the inner domain (ID) of gp120 as an independent molecule that encapsulates the A32-like region within a minimal structural unit of the HIV-1 Env. Through structure-based design, we developed ID2, which consists of the ID expressed independently of the outer domain and stabilized in the CD4-bound conformation by an inter-layer disulfide bond. ID2 expresses C1-C2 epitopes in the context of CD4-triggered full-length gp120 but without any known neutralizing epitope present. Thus, ID2 represents a novel probe for the analysis and/or selective induction of antibody responses to the A32 epitope region. We also present the crystal structure of ID2 complexed with mAb A32, which defines its epitope.

PubMed: 27041594
DOI: 10.1016/j.str.2016.03.005

Experimental method

X-RAY DIFFRACTION (3.1 Å)