2LP7

Structure of gp41-M-MAT, a membrane associated MPER trimer from HIV-1 gp41.

Summary for 2LP7

• Entry DOI: 10.2210/pdb2lp7/pdb
• NMR Information: BMRB: 18237
• Descriptor: Envelope glycoprotein (1 entity in total)
• Functional Keywords: gp41, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 3
• Total formula weight: 21032.43

Authors

Reardon, P.N. (deposition date: 2012-02-03, release date: 2013-02-06, Last modification date: 2024-05-15)

Primary citation

Reardon, P.N.,Sage, H.,Dennison, S.M.,Martin, J.W.,Donald, B.R.,Alam, S.M.,Haynes, B.F.,Spicer, L.D.
Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer.
Proc.Natl.Acad.Sci.USA, 111:1391-1396, 2014

PubMed Abstract: 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.

PubMed: 24474763
DOI: 10.1073/pnas.1309842111

Experimental method

SOLUTION NMR