Skip to main content
Journal cover image

Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.

Publication ,  Journal Article
Reardon, PN; Sage, H; Dennison, SM; Martin, JW; Donald, BR; Alam, SM; Haynes, BF; Spicer, LD
Published in: Proc Natl Acad Sci U S A
January 28, 2014

The membrane proximal external region (MPER) of HIV-1 glycoprotein (gp) 41 is involved in viral-host cell membrane fusion. It contains short amino acid sequences that are binding sites for the HIV-1 broadly neutralizing antibodies 2F5, 4E10, and 10E8, making these binding sites important targets for HIV-1 vaccine development. We report a high-resolution structure of a designed MPER trimer assembled on a detergent micelle. The NMR solution structure of this trimeric domain, designated gp41-M-MAT, shows that the three MPER peptides each adopt symmetric α-helical conformations exposing the amino acid side chains of the antibody binding sites. The helices are closely associated at their N termini, bend between the 2F5 and 4E10 epitopes, and gradually separate toward the C termini, where they associate with the membrane. The mAbs 2F5 and 4E10 bind gp41-M-MAT with nanomolar affinities, consistent with the substantial exposure of their respective epitopes in the trimer structure. The traditional structure determination of gp41-M-MAT using the Xplor-NIH protocol was validated by independently determining the structure using the DISCO sparse-data protocol, which exploits geometric arrangement algorithms that guarantee to compute all structures and assignments that satisfy the data.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 28, 2014

Volume

111

Issue

4

Start / End Page

1391 / 1396

Location

United States

Related Subject Headings

  • Molecular Sequence Data
  • Models, Molecular
  • Magnetic Resonance Spectroscopy
  • HIV-1
  • HIV Envelope Protein gp41
  • Biopolymers
  • Antibodies, Neutralizing
  • Amino Acid Sequence
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Reardon, P. N., Sage, H., Dennison, S. M., Martin, J. W., Donald, B. R., Alam, S. M., … Spicer, L. D. (2014). Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer. Proc Natl Acad Sci U S A, 111(4), 1391–1396. https://doi.org/10.1073/pnas.1309842111
Reardon, Patrick N., Harvey Sage, S Moses Dennison, Jeffrey W. Martin, Bruce R. Donald, S Munir Alam, Barton F. Haynes, and Leonard D. Spicer. “Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.Proc Natl Acad Sci U S A 111, no. 4 (January 28, 2014): 1391–96. https://doi.org/10.1073/pnas.1309842111.
Reardon PN, Sage H, Dennison SM, Martin JW, Donald BR, Alam SM, et al. Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer. Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1391–6.
Reardon, Patrick N., et al. “Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.Proc Natl Acad Sci U S A, vol. 111, no. 4, Jan. 2014, pp. 1391–96. Pubmed, doi:10.1073/pnas.1309842111.
Reardon PN, Sage H, Dennison SM, Martin JW, Donald BR, Alam SM, Haynes BF, Spicer LD. Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer. Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1391–1396.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 28, 2014

Volume

111

Issue

4

Start / End Page

1391 / 1396

Location

United States

Related Subject Headings

  • Molecular Sequence Data
  • Models, Molecular
  • Magnetic Resonance Spectroscopy
  • HIV-1
  • HIV Envelope Protein gp41
  • Biopolymers
  • Antibodies, Neutralizing
  • Amino Acid Sequence