Trimerization of the HIV Transmembrane Domain in Lipid Bilayers Modulates Broadly Neutralizing Antibody Binding
- 주제(키워드) Antibodies , HIV , Membrane proteins , Nanostructures , Peptides
- 등재 SCIE, SCOPUS
- 발행기관 Wiley-VCH Verlag
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000123989
- 본문언어 영어
- Published As http://dx.doi.org/10.1002/anie.201508421
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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