8B6Y

NMR assignment and structure of a peptide derived from the membrane proximal external region of HIV-1 gp41 in the presence of hexafluoroisopropanol

Summary for 8B6Y

• Entry DOI: 10.2210/pdb8b6y/pdb
• NMR Information: BMRB: 51531
• Descriptor: Envelope glycoprotein gp160 (1 entity in total)
• Functional Keywords: envelope glycoprotein, hiv-1, epitope, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 3219.97

Authors

Jimenez, M.A.,Partida-Hanon, A.,Nieva, J.L. (deposition date: 2022-09-27, release date: 2022-12-07, Last modification date: 2024-06-19)

Primary citation

Torralba, J.,de la Arada, I.,Partida-Hanon, A.,Rujas, E.,Arribas, M.,Insausti, S.,Valotteau, C.,Valle, J.,Andreu, D.,Caaveiro, J.M.M.,Jimenez, M.A.,Apellaniz, B.,Redondo-Morata, L.,Nieva, J.L.
Molecular recognition of a membrane-anchored HIV-1 pan-neutralizing epitope.
Commun Biol, 5:1265-1265, 2022

PubMed Abstract: Antibodies against the carboxy-terminal section of the membrane-proximal external region (C-MPER) of the HIV-1 envelope glycoprotein (Env) are considered as nearly pan-neutralizing. Development of vaccines capable of producing analogous broadly neutralizing antibodies requires deep understanding of the mechanism that underlies C-MPER recognition in membranes. Here, we use the archetypic 10E8 antibody and a variety of biophysical techniques including single-molecule approaches to study the molecular recognition of C-MPER in membrane mimetics. In contrast to the assumption that an interfacial MPER helix embodies the entire C-MPER epitope recognized by 10E8, our data indicate that transmembrane domain (TMD) residues contribute to binding affinity and specificity. Moreover, anchoring to membrane the helical C-MPER epitope through the TMD augments antibody binding affinity and relieves the effects exerted by the interfacial MPER helix on the mechanical stability of the lipid bilayer. These observations support that addition of TMD residues may result in more efficient and stable anti-MPER vaccines.

PubMed: 36400835
DOI: 10.1038/s42003-022-04219-6

Experimental method

SOLUTION NMR