title: Trimerization of the HIV Transmembrane Domain in Lipid Bilayers Modulates Broadly Neutralizing Antibody Binding.
abstract: The membrane-proximal external region (MPER) of HIV gp41 is an established target of antibodies that neutralize a broad range of HIV isolates. To evaluate the role of the transmembrane (TM) domain, synthetic MPER-derived peptides were incorporated into lipid nanoparticles using natural and designed TM domains, and antibody affinity was measured using immobilized and solution-based techniques. Peptides incorporating the native HIV TM domain exhibit significantly stronger interactions with neutralizing antibodies than peptides with a monomeric TM domain. Furthermore, a peptide with a trimeric, three-helix bundle TM domain recapitulates the binding profile of the native sequence. These studies suggest that neutralizing antibodies can bind the MPER when the TM domain is a three-helix bundle and this presentation could influence the binding of neutralizing antibodies to the virus. Lipid-bilayer presentation of viral antigens in Nanodiscs is a new platform for evaluating neutralizing antibodies.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Reichart
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.|School of Chemistry & Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Baksh
authors.affiliation: Department of Food Science and Engineering, Ewha Womans University, Seoul, 03760, Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Rhee
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Fiedler
authors.affiliation: Department of Biochemistry, University of Illinois, Urbana, IL, 61801, USA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Sligar
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.|School of Chemistry & Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Zwick
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Dawson
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D001704:Biopolymers / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000276:immunology; D008051:Lipid Bilayers
chemical_list: D057134:Antibodies, Neutralizing; D001704:Biopolymers; D015700:HIV Envelope Protein gp41; D008051:Lipid Bilayers
keywords: HIV; antibodies; membrane proteins; nanostructures; peptides