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Trimerization of the HIV Transmembrane Domain in Lipid Bilayers Modulates Broadly Neutralizing Antibody Binding
Author(s) -
Reichart Timothy M.,
Baksh Michael M.,
Rhee JinKyu,
Fiedler Jason D.,
Sligar Stephen G.,
Finn M. G.,
Zwick Michael B.,
Dawson Philip E.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201508421
Subject(s) - gp41 , lipid bilayer , chemistry , antibody , transmembrane domain , biophysics , peptide , helix bundle , transmembrane protein , neutralizing antibody , bilayer , virology , membrane , protein structure , virus , biochemistry , biology , epitope , receptor , immunology
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.