Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Measles virus poses a significant global health threat.
• Three cell receptors for measles virus are known, with two structures solved.
• The binding mechanism of nectin-4, an epithelial cell receptor, to measles virus hemagglutinin (MV-H) was previously unknown.

Purpose of the Study:

• To determine the structural basis of nectin-4 binding to MV-H.
• To identify potential therapeutic targets for measles virus infection.

Main Methods:

• X-ray crystallography was used to solve the structure of the membrane-distal domain of human nectin-4 in complex with MV-H.
• Structural analysis focused on the interaction interface and binding site.

Main Results:

• The structure revealed that nectin-4 binds exclusively to the MV-H β4-β5 groove via its N-terminal IgV domain.
• Hydrophobic interactions dominate the nectin-4/MV-H binding interface.
• The MV-H binding site for nectin-4 overlaps with those of previously identified receptors.
• A conserved hydrophobic pocket within the MV-H β4-β5 groove is implicated in binding all three known measles virus receptors.

Conclusions:

• The study provides the first structural insights into nectin-4 and MV-H interaction.
• The identified conserved hydrophobic pocket represents a promising target for broad-spectrum antiviral drug development against measles virus.