Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1
Author Information
Author(s): Di Giovine Paolo, Settembre Ethan C., Bhargava Arjun K., Luftig Micah A., Lou Huan, Cohen Gary H., Eisenberg Roselyn J., Krummenacher Claude, Carfi Andrea
Primary Institution: Department of Biochemistry and Molecular Biology, IRBM P. Angeletti, Pomezia, Rome, Italy
Hypothesis
The study aims to elucidate the molecular basis for the interaction between herpes simplex virus glycoprotein D (gD) and its cellular receptor nectin-1.
Conclusion
The structure of the gD/Nectin-1 complex reveals how gD binding triggers conformational changes that facilitate herpes simplex virus entry into host cells.
Supporting Evidence
- The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor.
- Mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry.
- The gD/Nectin-1 structure shows that gD binding interferes with nectin-1's ability to mediate cell adhesion.
- Comparison with previous structures suggests a common mechanism for receptor-mediated activation of HSV entry.
Takeaway
This study shows how a virus uses a special protein to grab onto a human cell, which helps it get inside and cause infection.
Methodology
The structure was determined using x-ray crystallography to 4.0 Å resolution.
Limitations
The study does not address the dynamic nature of the gD/Nectin-1 interaction in a physiological context.
Digital Object Identifier (DOI)
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