Deciphering Bacteriophage T5 Host Recognition Mechanism and Infection Trigger.

Area of Science:

• Virology
• Structural Biology
• Microbiology

Background:

• Bacteriophages (phages) are viruses that infect bacteria.
• Phages utilize receptor binding proteins (RBPs) for host recognition, a critical step in infection.
• The precise molecular mechanisms of RBP-host interaction remain largely uncharacterized for most phages.

Purpose of the Study:

• To determine the cryo-electron microscopy (cryo-EM) structure of bacteriophage T5's RBP (RBPpb5) bound to its Escherichia coli receptor, FhuA.
• To elucidate the molecular details of RBP-protein receptor interaction and its role in initiating phage infection.
• To propose a mechanism for signal transmission from receptor binding to downstream infection events.

Main Methods:

• Electron cryo-microscopy (cryo-EM) to determine the structure of the RBPpb5-FhuA complex.
• Structural analysis of the RBPpb5 within the complex.
• Comparison with AlphaFold2-predicted structures.
• Integration with existing cryo-EM data of the T5 tail tip.

Main Results:

• The cryo-EM structure of the monomeric RBPpb5 in complex with the FhuA receptor was determined.
• The structure provides insights into the irreversible binding of RBPpb5 to FhuA, committing the phage to infection.
• A model for the transmission of the binding event to the phage's tail fiber, initiating DNA ejection, was proposed.

Conclusions:

• This study presents the first structure of a phage RBP bound to a protein receptor (FhuA).
• The findings reveal the molecular basis of host recognition by bacteriophage T5.
• The proposed mechanism sheds light on how RBP binding triggers subsequent infection steps, including DNA delivery into the host cytoplasm.