DOI: 10.1128/jvi.78.19.10724-10737.2004. Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope

Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope

10.1128/jvi.78.19.10724-10737.2004

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT The membrane-proximal region of the ectodomain of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the target of three of the five broadly neutralizing anti-HIV-1 antibodies thus far isolated. We have determined crystal structures of the antigen-binding fragment for one of these antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides of the gp41 membrane-proximal region, at 2.0-, 2.1-, and 2.2-Å resolutions, respectively. The structures reveal an extended gp41 conformation, which stretches over 30 Å in length. Contacts are made with five complementarity-determining regions of the antibody as well as with nonpolymorphic regions. Only one exclusive charged face of the gp41 epitope is bound by 2F5, while the nonbound face, which is hydrophobic, may be hidden due to occlusion by other portions of the ectodomain. The structures reveal that the 2F5 antibody is uniquely built to bind to an epitope that is proximal to a membrane surface and in a manner mostly unaffected by large-scale steric hindrance. Biochemical studies with proteoliposomes confirm the importance of lipid membrane and hydrophobic context in the binding of 2F5 as well as in the binding of 4E10, another broadly neutralizing antibody that recognizes the membrane-proximal region of gp41. Based on these structural and biochemical results, immunization strategies for eliciting 2F5- and 4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed.

Bibliography

Ofek, G., Tang, M., Sambor, A., Katinger, H., Mascola, J. R., Wyatt, R., & Kwong, P. D. (2004). Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope. Journal of Virology, 78(19), 10724â10737.

Authors 7

Gilad Ofek (first)
Min Tang (additional)
Anna Sambor (additional)
Hermann Katinger (additional)
John R. Mascola (additional)
Richard Wyatt (additional)
Peter D. Kwong (additional)

References 68 Referenced 403

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Dates

Type	When
Created	20 years, 11 months ago (Sept. 14, 2004, 4:48 p.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 3:42 a.m.)
Indexed	1 month, 4 weeks ago (July 3, 2025, 2:03 p.m.)
Issued	20 years, 11 months ago (Oct. 1, 2004)
Published	20 years, 11 months ago (Oct. 1, 2004)
Published Print	20 years, 11 months ago (Oct. 1, 2004)

Funders 0

None

BibTeX

@article{Ofek_2004, title={Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope}, volume={78}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.78.19.10724-10737.2004}, DOI={10.1128/jvi.78.19.10724-10737.2004}, number={19}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Ofek, Gilad and Tang, Min and Sambor, Anna and Katinger, Hermann and Mascola, John R. and Wyatt, Richard and Kwong, Peter D.}, year={2004}, month=oct, pages={10724–10737} }

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