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Crystallographic and cryo EM analysis of virion-receptor interactions
M G Rossmann1, N H Olson, P R Kolatkar
1Department of Biological Sciences, Purdue University, West Lafayette, Indiana.
Insights
Researchers used cryoelectron microscopy to visualize the first virus-glycoprotein receptor complex. Human rhinovirus 16 (HRV16) binds to intercellular adhesion molecule-1 (ICAM-1) within a surface "canyon," blocking antibody access.
Area of Science:
- Structural biology
- Virology
- Molecular interactions
Background:
- Viruses utilize cellular receptors for entry.
- Understanding virus-receptor interactions is crucial for antiviral strategies.
- Previous studies predicted receptor binding sites in viral surface cavities.
Purpose of the Study:
- To determine the first high-resolution structure of a virus complexed with its cellular receptor.
- To elucidate the binding mechanism between Human Rhinovirus 16 (HRV16) and intercellular adhesion molecule-1 (ICAM-1).
Main Methods:
- Cryoelectron microscopy was employed to obtain the structural data.
- The study involved complexing HRV16 with the relevant domains of ICAM-1.
- Atomic structures of homologous viral and receptor proteins (HRV14 and CD4) were used for comparison.
Main Results:
- The structure revealed that ICAM-1 binds within a 12 Å deep "canyon" on the HRV16 surface.
- This binding site is inaccessible to host antibodies, supporting prior predictions.
- Observed densities showed excellent correspondence with homologous HRV14 and CD4 structures, validating the interaction model.
Conclusions:
- The determined structure provides the first atomic-level view of a virus-glycoprotein receptor complex.
- The findings confirm the "canyon" hypothesis for viral attachment sites, offering insights into immune evasion.
- This structural information is vital for developing targeted antiviral therapies against rhinoviruses.
Abstract:
Cryoelectron microscopy has been used to determine the first structure of a virus when complexed with its glycoprotein cellular receptor. Human rhinovirus 16 (HRV16) complexed with the two amino-terminal, immunoglobulin-like domains of the intercellular adhesion molecule-1 (ICAM-1) shows that ICAM-1 binds into the 12 A deep "canyon" on the surface of the virus. This is consistent with the prediction that the viral receptor attachment site lies in a cavity inaccessible to the host's antibodies. The atomic structures of HRV14 and CD4, homologous to HRV16 and ICAM-1, showed excellent correspondence with observed density, thus establishing the virus-receptor interactions.