4RFO

Crystal structure of the ADCC-Potent Antibody N60-I3 Fab in complex with HIV-1 Clade A/E gp120 and M48u1

Summary for 4RFO

• Entry DOI: 10.2210/pdb4rfo/pdb
• Related: 4H8W 4JZW 4RFE 4RFN
• Related PRD ID: PRD_001094
• Descriptor: HIV-1 clade A/E gp120, m48u1 CD4 mimetic peptide, N60-i3 Fab heavy chain, ... (6 entities in total)
• Functional Keywords: hiv-1 gp120, clade a/e 93th057, viral protein, viral protein-immune system-inhibitor complex, viral protein/immune system/inhibitor
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 4
• Total formula weight: 91963.12

Authors

Tolbert, W.D.,Gohain, N.,Pazgier, M. (deposition date: 2014-09-26, release date: 2015-07-15, Last modification date: 2023-12-06)

Primary citation

Gohain, N.,Tolbert, W.D.,Acharya, P.,Yu, L.,Liu, T.,Zhao, P.,Orlandi, C.,Visciano, M.L.,Kamin-Lewis, R.,Sajadi, M.M.,Martin, L.,Robinson, J.E.,Kwong, P.D.,DeVico, A.L.,Ray, K.,Lewis, G.K.,Pazgier, M.
Cocrystal Structures of Antibody N60-i3 and Antibody JR4 in Complex with gp120 Define More Cluster A Epitopes Involved in Effective Antibody-Dependent Effector Function against HIV-1.
J.Virol., 89:8840-8854, 2015

PubMed Abstract: Accumulating evidence indicates a role for Fc receptor (FcR)-mediated effector functions of antibodies, including antibody-dependent cell-mediated cytotoxicity (ADCC), in prevention of human immunodeficiency virus type 1 (HIV-1) acquisition and in postinfection control of viremia. Consequently, an understanding of the molecular basis for Env epitopes that constitute effective ADCC targets is of fundamental interest for humoral anti-HIV-1 immunity and for HIV-1 vaccine design. A substantial portion of FcR effector function of potentially protective anti-HIV-1 antibodies is directed toward nonneutralizing, transitional, CD4-inducible (CD4i) epitopes associated with the gp41-reactive region of gp120 (cluster A epitopes). Our previous studies defined the A32-like epitope within the cluster A region and mapped it to the highly conserved and mobile layers 1 and 2 of the gp120 inner domain within the C1-C2 regions of gp120. Here, we elucidate additional cluster A epitope structures, including an A32-like epitope, recognized by human monoclonal antibody (MAb) N60-i3, and a hybrid A32-C11-like epitope, recognized by rhesus macaque MAb JR4. These studies define for the first time a hybrid A32-C11-like epitope and map it to elements of both the A32-like subregion and the seven-layered β-sheet of the gp41-interactive region of gp120. These studies provide additional evidence that effective antibody-dependent effector function in the cluster A region depends on precise epitope targeting--a combination of epitope footprint and mode of antibody attachment. All together these findings help further an understanding of how cluster A epitopes are targeted by humoral responses.

PubMed: 26085162
DOI: 10.1128/JVI.01232-15

Experimental method

X-RAY DIFFRACTION (3.2 Å)