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Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion.(BIOPHYSICS AND COMPUTATIONAL BIOLOGY)(Report)

Zeng, Xiancheng ; Mukhopadhyay, Suchetana ; Brooks, Charles L., III

Proceedings of the National Academy of Sciences of the United States, Feb 17, 2015, Vol.112(7), p.2034 [Peer Reviewed Journal]

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  • Title:
    Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion.(BIOPHYSICS AND COMPUTATIONAL BIOLOGY)(Report)
  • Author: Zeng, Xiancheng ; Mukhopadhyay, Suchetana ; Brooks, Charles L., III
  • Subjects: RNA Viruses – Genetic Aspects ; Viral Proteins – Properties ; Virulence (Microbiology) – Genetic Aspects ; Protein-Protein Interactions – Observations
  • Is Part Of: Proceedings of the National Academy of Sciences of the United States, Feb 17, 2015, Vol.112(7), p.2034
  • Description: Alphavirus envelope proteins, organized as trimers of E2-E1 heterodimers on the surface of the pathogenic alphavirus, mediate the low pH-triggered fusion of viral and endosomal membranes in human cells. The lack of specific treatment for alphaviral infections motivates our exploration of potential antiviral approaches by inhibiting one or more fusion steps in the common endocytic viral entry pathway. In this work, we performed constant pH molecular dynamics based on an atomic model of the alphavirus envelope with icosahedral symmetry. We have identified pH-sensitive residues that cause the largest shifts in thermodynamic driving forces under neutral and acidic pH conditions for various fusion steps. A series of conserved interdomain His residues is identified to be responsible for the pH-dependent conformational changes in the fusion process, and ligand binding sites in their vicinity are anticipated to be potential drug targets aimed at inhibiting viral infections. alphavirus | envelope protein | pH | membrane fusion | constant pH molecular dynamics
  • Language: English
  • Identifier: ISSN: 0027-8424
  • Source: Cengage Learning, Inc.

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