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.
Bibliographical noteFunding Information:
This research was supported by the California HIV/AIDS Research Grants Program, D10-SRI-30 (T.M.R.), International AIDS Vaccine Initiative (P.E.D.), and NIH EB015663 (M.G.F.), GM33775 (S.G.S.), AI114401 (M.B.Z.), and GM098871 (P.E.D.). We thank V. Mitch Luna, C. David Stout, Johannes S. Gach, Arthur S. Kim and Florence Brunel for assistance and advice.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
- membrane proteins