Sequence-dependent backbone dynamics of a viral fusogen transmembrane helix

Area of Science:

• Biophysics
• Structural Biology
• Virology

Background:

• Transmembrane domains of viral fusogenic proteins are critical for lipid bilayer mixing.
• Previous studies indicated that specific mutations compromise the fusogenicity of the Vesicular Stomatitis virus G-protein transmembrane helix.

Purpose of the Study:

• To investigate the relationship between backbone dynamics and fusogenicity of viral fusogenic transmembrane helices.
• To determine if mutations affecting fusogenicity also alter helix backbone dynamics.

Main Methods:

• Deuterium/hydrogen-exchange kinetics were used to measure backbone dynamics.
• Analysis focused on mutations within a GxxxG motif and Ile residues of the Vesicular Stomatitis virus G-protein transmembrane helix.

Main Results:

• Mutations previously shown to compromise fusogenicity reduced the backbone dynamics of the transmembrane helix.
• The observed reduction in backbone dynamics supports a link between dynamics and fusogenicity.
• Glycine and Isoleucine residues are over-represented in viral fusogen transmembrane helices, consistent with findings.

Conclusions:

• Backbone dynamics of viral fusogenic transmembrane helices are linked to their fusogenicity.
• Protein sequence, backbone dynamics, and fusogenicity of transmembrane segments are interrelated.