Distinctive Membrane Accommodation Traits Underpinning the Neutralization Activity of HIV-1 Antibody against MPER DOI Creative Commons
Cármen Domene, Brian Wiley, Sara Insausti

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

The membrane-proximal external region (MPER), located in the carboxy-terminal section of HIV's envelope glycoprotein (Env) ectodomain, which is essential for viral entry into host cells, has gained considerable attention as a target HIV vaccine development due to exceptional neutralization breadth antibodies against MPER epitopes. A distinctive feature broadly neutralizing (bnAbs) targeting their requirement accommodate membrane surface antigen-binding fragment, or Fab moiety, optimize antigen recognition. In this study, we sought elucidate molecular mechanism behind interaction and its relevance antiviral function bnAb 10E8. We conducted all-atom dynamics simulations three systems: (i) 10E8 positioned on viral-like lipid bilayer (VL-LB), (ii) complex with an helix anchored VL-LB via Env transmembrane domain (TMD), (iii) Fab/MPER-TMD similarly embedded but chemically optimized variant showing enhanced potency. Comparing these systems enabled us derive atomic-scale Fab-membrane accommodation profiles pertinent 10E8's function. Our findings support that adaptation interface following epitope binding crucial developing MPER-targeted activity. This analysis also provides insights pathways strengthening interactions, may prove valuable designing MPER-based biologics vaccines prevent treat infection.

Language: Английский

Distinctive Membrane Accommodation Traits Underpinning the Neutralization Activity of HIV-1 Antibody against MPER DOI Creative Commons
Cármen Domene, Brian Wiley, Sara Insausti

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

The membrane-proximal external region (MPER), located in the carboxy-terminal section of HIV's envelope glycoprotein (Env) ectodomain, which is essential for viral entry into host cells, has gained considerable attention as a target HIV vaccine development due to exceptional neutralization breadth antibodies against MPER epitopes. A distinctive feature broadly neutralizing (bnAbs) targeting their requirement accommodate membrane surface antigen-binding fragment, or Fab moiety, optimize antigen recognition. In this study, we sought elucidate molecular mechanism behind interaction and its relevance antiviral function bnAb 10E8. We conducted all-atom dynamics simulations three systems: (i) 10E8 positioned on viral-like lipid bilayer (VL-LB), (ii) complex with an helix anchored VL-LB via Env transmembrane domain (TMD), (iii) Fab/MPER-TMD similarly embedded but chemically optimized variant showing enhanced potency. Comparing these systems enabled us derive atomic-scale Fab-membrane accommodation profiles pertinent 10E8's function. Our findings support that adaptation interface following epitope binding crucial developing MPER-targeted activity. This analysis also provides insights pathways strengthening interactions, may prove valuable designing MPER-based biologics vaccines prevent treat infection.

Language: Английский

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