Exploring Structural Diversity among Adhesion Devices Encoded by Lactococcal P335 Phages with AlphaFold2

Area of Science:

• Microbiology
• Structural Biology
• Bioinformatics

Background:

• Bacteriophages (phages) are abundant biological entities with sophisticated nanodevices for bacterial infection.
• Phage infection begins with specific adhesion to host cell surfaces, a process mediated by diverse and often poorly understood adhesion devices in siphophages infecting Gram-positive bacteria.
• The complex, multi-domain nature of these adhesion proteins challenges traditional experimental structural analyses.

Purpose of the Study:

• To predict the structures of adhesion devices from P335 group siphages that infect *Lactococcus* spp.
• To elucidate the structural diversity and potential functional mechanisms of these phage adhesion systems.
• To leverage AlphaFold2 for detailed structural insights into complex phage-bacterial interaction machinery.

Main Methods:

• Utilized the AlphaFold2 protein structure prediction program.
• Generated structure predictions for adhesion devices from representative types I-IV P335 siphages.
• Analyzed predicted structures to understand topology and potential functional implications.

Main Results:

• Predicted structures revealed significant topological diversity among P335 group siphage adhesion devices.
• Adhesion devices from types III and IV P335 phages exhibited a topology similar to *Skunavirus* p2.
• This structural similarity suggests a conserved activation mechanism involving a receptor binding protein and a distal tail protein loop.

Conclusions:

• AlphaFold2 is effective in predicting structures of complex phage adhesion devices.
• P335 group siphages display diverse adhesion device architectures.
• A conserved mechanism for host cell surface recognition and binding activation may exist among certain siphage groups.