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Insertion and Anchoring of HIV-1 Fusion Peptide into Complex Membrane Mimicking Human T-cell.
Zhao, Mingfei; Lopes, Laura Joana Silva; Sahni, Harshita; Yadav, Anju; Do, Hung N; Reddy, Tyler; López, Cesar A; Neale, Chris; Gnanakaran, S.
Afiliación
  • Zhao M; T-6 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos NM USA.
  • Lopes LJS; T-6 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos NM USA.
  • Sahni H; T-6 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos NM USA.
  • Yadav A; Department of Computer Science, University of New Mexico, Albuquerque NM, USA.
  • Do HN; T-6 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos NM USA.
  • Reddy T; Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso TX, USA.
  • López CA; T-6 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos NM USA.
  • Neale C; CCS-7 Applied Computer Science Group, Los Alamos National Laboratory, Los Alamos NM USA.
  • Gnanakaran S; T-6 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos NM USA.
bioRxiv ; 2024 Aug 04.
Article en En | MEDLINE | ID: mdl-39131401
ABSTRACT
A fundamental understanding of how HIV-1 envelope (Env) protein facilitates fusion is still lacking. The HIV-1 fusion peptide, consisting of 15 to 22 residues, is the N-terminus of the gp41 subunit of the Env protein. Further, this peptide, a promising vaccine candidate, initiates viral entry into target cells by inserting and anchoring into human immune cells. The influence of membrane lipid reorganization and the conformational changes of the fusion peptide during the membrane insertion and anchoring processes, which can significantly affect HIV-1 cell entry, remains largely unexplored due to the limitations of experimental measurements. In this work, we investigate the insertion of the fusion peptide into an immune cell membrane mimic through multiscale molecular dynamics simulations. We mimic the native T-cell by constructing a 9-lipid asymmetric membrane, along with geometrical restraints accounting for insertion in the context of gp41. To account for the slow timescale of lipid mixing while enabling conformational changes, we implement a protocol to go back and forth between atomistic and coarse-grained simulations. Our study provides a molecular understanding of the interactions between the HIV-1 fusion peptide and the T-cell membrane, highlighting the importance of conformational flexibility of fusion peptides and local lipid reorganization in stabilizing the anchoring of gp41 into the targeted host membrane during the early events of HIV-1 cell entry. Importantly, we identify a motif within the fusion peptide critical for fusion that can be further manipulated in future immunological studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos