HIV-1 Broadly Neutralizing Antibody Extracts Its Epitope from a Kinked gp41 Ectodomain Region on the Viral Membrane

Zhen Yu J Sun, Kyoung Joon Oh, Mikyung Kim, Jessica Yu, Vladimir Brusic, Likai Song, Zhisong Qiao, Jia huai Wang, Gerhard Wagner, Ellis L. Reinherz

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

Although rarely elicited during natural human infection, the most broadly neutralizing antibodies (BNAbs) against diverse human immunodeficiency virus (HIV)-1 strains target the membrane-proximal ectodomain region (MPER) of viral gp41. To gain insight into MPER antigenicity, immunogenicity, and viral function, we studied its structure in the lipid environment by a combination of nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and surface plasmon resonance (SPR) techniques. The analyses revealed a tilted N-terminal α helix (aa 664-672) connected via a short hinge to a flat C-terminal helical segment (675-683). This metastable L-shaped structure is immersed in viral membrane and, therefore, less accessible to immune attack. Nonetheless, the 4E10 BNAb extracts buried W672 and F673 after initial encounter with the surface-embedded MPER. The data suggest how BNAbs may perturb tryptophan residue-associated viral fusion involving the mobile N-terminal MPER segment and, given conservation of MPER sequences in HIV-1, HIV-2, and SIV, have important implications for structure-guided vaccine design.

Original languageEnglish
Pages (from-to)52-63
Number of pages12
JournalImmunity
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 18 2008
Externally publishedYes

Fingerprint

Neutralizing Antibodies
HIV-1
Epitopes
Membranes
HIV-2
Surface Plasmon Resonance
Electron Spin Resonance Spectroscopy
Tryptophan
Magnetic Resonance Spectroscopy
Vaccines
Lipids
Infection

Keywords

  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

HIV-1 Broadly Neutralizing Antibody Extracts Its Epitope from a Kinked gp41 Ectodomain Region on the Viral Membrane. / Sun, Zhen Yu J; Oh, Kyoung Joon; Kim, Mikyung; Yu, Jessica; Brusic, Vladimir; Song, Likai; Qiao, Zhisong; Wang, Jia huai; Wagner, Gerhard; Reinherz, Ellis L.

In: Immunity, Vol. 28, No. 1, 18.01.2008, p. 52-63.

Research output: Contribution to journalArticle

Sun, ZYJ, Oh, KJ, Kim, M, Yu, J, Brusic, V, Song, L, Qiao, Z, Wang, JH, Wagner, G & Reinherz, EL 2008, 'HIV-1 Broadly Neutralizing Antibody Extracts Its Epitope from a Kinked gp41 Ectodomain Region on the Viral Membrane', Immunity, vol. 28, no. 1, pp. 52-63. https://doi.org/10.1016/j.immuni.2007.11.018
Sun, Zhen Yu J ; Oh, Kyoung Joon ; Kim, Mikyung ; Yu, Jessica ; Brusic, Vladimir ; Song, Likai ; Qiao, Zhisong ; Wang, Jia huai ; Wagner, Gerhard ; Reinherz, Ellis L. / HIV-1 Broadly Neutralizing Antibody Extracts Its Epitope from a Kinked gp41 Ectodomain Region on the Viral Membrane. In: Immunity. 2008 ; Vol. 28, No. 1. pp. 52-63.
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