A two-step mechanism for the binding of the HIV-1 MPER epitope by the 10E8 antibody onto biosensor-supported lipid bilayers.

Autor: García-Porras M; Instituto Biofisika (CSIC-UPV/EHU), University of the Basque Country (UPV/EHU), Bilbao, Spain., Torralba J; Instituto Biofisika (CSIC-UPV/EHU), University of the Basque Country (UPV/EHU), Bilbao, Spain.; Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Bilbao, Spain., Insausti S; Instituto Biofisika (CSIC-UPV/EHU), University of the Basque Country (UPV/EHU), Bilbao, Spain.; Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Bilbao, Spain., Valle J; Laboratory of Proteomics and Protein Chemistry, Department of Medicine and Life Sciences, Pompeu Fabra University, Barcelona, Spain., Andreu D; Laboratory of Proteomics and Protein Chemistry, Department of Medicine and Life Sciences, Pompeu Fabra University, Barcelona, Spain., Apellániz B; Department of Physiology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain., Nieva JL; Instituto Biofisika (CSIC-UPV/EHU), University of the Basque Country (UPV/EHU), Bilbao, Spain.; Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Bilbao, Spain.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2024 Apr; Vol. 598 (7), pp. 787-800. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1002/1873-3468.14814
Abstrakt: HIV-1 antibodies targeting the carboxy-terminal area of the membrane-proximal external region (ctMPER) are close to exerting viral pan-neutralization. Here, we reconstituted the ctMPER epitope as the N-terminal extremity of the Env glycoprotein transmembrane domain helix and immobilized it onto biosensor-supported lipid bilayers. We assessed the binding mechanism of anti-MPER antibody 10E8 through Surface Plasmon Resonance, and found, through equilibrium and kinetic binding analyses as a function of bilayer thickness, peptide length, and paratope mutations, that 10E8 engages first with the epitope peptide (encounter), limited by ctMPER helix accessibility at the membrane surface, and then inserts into the lipid bilayer assisted by favorable Fab-membrane interactions (docking). This mechanistic information may help in devising new strategies to develop more efficient MPER-targeting vaccines.
(© 2024 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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