Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Measles virus (MeV) is a significant global cause of childhood illness and death.
• MeV primarily infects immune cells by utilizing the signaling lymphocyte activation molecule (SLAM) as its cellular receptor.
• Understanding the interaction between MeV and SLAM is crucial for developing effective antiviral strategies.

Purpose of the Study:

• To determine the crystal structure of the measles virus hemagglutinin (MV-H) protein in complex with its receptor, SLAM.
• To elucidate the molecular mechanism of MeV attachment to host cells.
• To provide a structural basis for understanding MeV-SLAM interactions and inform antiviral drug design.

Main Methods:

• X-ray crystallography was employed to obtain high-resolution structures of the MV-H ectodomain in complex with SLAM.
• Structural analysis focused on the binding interface between MV-H and SLAM, as well as the overall quaternary structure of the complex.

Main Results:

• The crystal structures revealed that the MV-H head domain binds to the membrane-distal ectodomain of SLAM via the side of its β-propeller fold.
• This binding mode differs from other paramyxoviruses, which typically use the top of their β-propeller domain for receptor attachment.
• Two distinct tetrameric assembly forms (dimer of dimers) of the MV-H-SLAM complex were observed, suggesting potential implications for fusion triggering.

Conclusions:

• The determined MV-H-SLAM structures offer valuable insights into the molecular basis of measles virus entry.
• These findings provide a structural template for designing novel antiviral drugs targeting MeV infection.
• The study also sheds light on the mechanism of homophilic SLAM-SLAM interactions involved in immune regulation and explains the efficacy of the measles vaccine.