Trimerization of the HIV Transmembrane Domain in Lipid Bilayers Modulates Broadly Neutralizing Antibody Binding

Timothy M. Reichart, Michael M. Baksh, Jin Kyu Rhee, Jason D. Fiedler, Stephen G. Sligar, M. G. Finn, Michael B. Zwick, Philip E. Dawson

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish
Pages (from-to)2688-2692
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number8
StatePublished - 18 Feb 2016

Bibliographical note

Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


  • HIV
  • antibodies
  • membrane proteins
  • nanostructures
  • peptides


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