@article{1cb83cc27bf24283b0fce4db1125737e,
title = "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",
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.",
author = "Tolbert, {William D.} and Neelakshi Gohain and Maxime Veillette and Chapleau, {Jean Philippe} and Chiara Orlandi and Visciano, {Maria L.} and Maryam Ebadi and DeVico, {Anthony L.} and Fouts, {Timothy R.} and Andr{\'e}s Finzi and Lewis, {George K.} and Marzena Pazgier",
note = "Funding Information: We thank our IHV colleagues for outstanding support of the studies leading to the ideas presented above, specifically Dr. Robert C. Gallo for his continued critical insights. This work was supported by NIAID , NIH grants: R01 AI116274 to M.P. and R01AI087181 to G.K.L., and a grant from The Bill and Melinda Gates Foundation : # OPP1033109 to G.K.L. We thank the FRQS-SIDA network, the CRCHUM Flow Cytometry Platform for technical assistance, and Mario Legault for cohort coordination. This work was partially supported by a Canada Foundation for Innovation Program Leader grant, by CIHR operating grants # 119334 and # 134117 to A.F., and by the FRQS AIDS and Infectious Diseases Network . A.F. is the recipient of a Canada Research Chair on Retroviral Entry. M.V. was supported by a CIHR Doctoral Research Award # 291485 . ID1 and ID2 concepts are Patent Pending. Dr. T.R.F. is an employee and shareholder of Profectus Biosciences. Drs. A.L.D. and G.K.L. are shareholders of Profectus Biosciences. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd. All rights reserved.",
year = "2016",
month = may,
day = "3",
doi = "10.1016/j.str.2016.03.005",
language = "English",
volume = "24",
pages = "697--709",
journal = "Structure",
issn = "0969-2126",
number = "5",
}