Sialoglycan binding triggers spike opening in a human coronavirus

Area of Science:

• Virology
• Structural Biology
• Immunology

Background:

• Coronavirus spike proteins are crucial for viral entry and are key targets for antibodies.
• Spike proteins of SARS-CoV, SARS-CoV-2, and MERS-CoV dynamically switch between open and closed states for host cell attachment and immune evasion.
• Most other coronavirus spike proteins are observed in a closed pre-fusion state, suggesting regulated opening.

Purpose of the Study:

• To investigate the conformational changes of the human coronavirus HKU1 spike protein upon receptor binding.
• To elucidate the mechanism by which receptor binding influences spike protein conformation and potential implications for viral entry and immune escape.

Main Methods:

• Cryogenic electron microscopy (cryo-EM) to determine high-resolution structures.
• Molecular dynamics (MD) simulations to analyze protein conformational dynamics.

Main Results:

• Human coronavirus HKU1 spike protein undergoes conformational changes after binding to a sialoglycan receptor on domain S1A.
• Receptor binding allosterically triggers the opening of domain S1B through interdomain communication.
• This opening mechanism differs from the spontaneous transitions observed in other betacoronaviruses.

Conclusions:

• Receptor-induced allosteric conformational changes in coronavirus spike proteins regulate viral attachment.
• The findings suggest a mechanism for immune evasion through controlled spike protein opening and potential dual receptor utilization.
• This study provides insights into the molecular basis of coronavirus entry and host-pathogen interactions.