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

Angewandte Chemie
Timothy M ReichartPhilip E Dawson

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.

References

Feb 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·H GratkowskiW F DeGrado
Mar 7, 2001·Science·M J RootP S Kim
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·D M Eckert, P S Kim
Mar 18, 2004·Journal of the American Chemical Society·I G DenisovS G Sligar
Dec 17, 2004·Journal of the American Chemical Society·Dmitry A MarkovDarryl J Bornhop
Mar 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Gary FreyBing Chen
Aug 1, 2008·Nature·Jun LiuSriram Subramaniam
May 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Likai SongMikyung Kim
Oct 20, 2009·FEBS Letters·Timothy H Bayburt, Stephen G Sligar
Nov 12, 2009·Methods in Enzymology·T K RitchieS G Sligar
Nov 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·S Munir AlamBing Chen
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Erin M SchererDennis R Burton
Oct 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·Dennis R Burton
Oct 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Shang-Rung WuHenrik Garoff
Feb 4, 2011·Chembiochem : a European Journal of Chemical Biology·Amanda KussrowM G Finn
Mar 2, 2011·The Journal of Experimental Medicine·Claudia R RuprechtAlexandra Trkola
Mar 15, 2011·Nature Biotechnology·Michael M BakshDarryl J Bornhop
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dennis R BurtonJohn P Moore
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Audray HarrisSriram Subramaniam
Aug 7, 2012·Nature Structural & Molecular Biology·Youdong MaoJoseph Sodroski
Nov 2, 2013·Science·Jean-Philippe JulienIan A Wilson
Jul 6, 2014·Science Translational Medicine·Amarendra PeguGary J Nabel
Nov 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Devin SokDennis R Burton
Jul 15, 2015·Science·John R Mascola

❮ Previous
Next ❯

Citations

Nov 5, 2016·ACS Applied Materials & Interfaces·Yadveer S GrewalMatt Trau
Feb 9, 2017·Chemical Reviews·Ilia G Denisov, Stephen G Sligar
Jun 9, 2016·Nature Structural & Molecular Biology·Ilia G Denisov, Stephen G Sligar
Jul 28, 2016·Biological Chemistry·Aldino ViegasManuel Etzkorn
Apr 20, 2017·Current Opinion in HIV and AIDS·Nichole CeruttiWinfried Weissenhorn
Jul 2, 2020·Viruses·Chelsea T Barrett, Rebecca Ellis Dutch
Mar 30, 2018·Current Opinion in Biotechnology·Steven FreyRavi S Kane
Dec 27, 2017·Journal of the American Chemical Society·Sai Chaitanya ChiliveriAd Bax

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.