Tail Fiber Classification Code

Phage tail fibers are structurally classified into 16 distinct classes and 89 domains using the RBPseg pipeline, which segments and models fibers based on structural features.

Overview of Tail Fiber Classification

Tail fibers are a major class of receptor-binding proteins (RBPs) in bacteriophages. They are typically elongated, flexible, and trimeric, making experimental resolution of their full-length structures challenging . To address this, the RBPseg pipeline uses deep learning-based protein structure prediction tools like ESMFold and AlphaFold2-multimer (AF2M) to segment tail fiber sequences into smaller, manageable fractions while preserving domain boundaries .

RBPseg Methodology

1. Monomeric Prediction: ESMFold predicts the monomeric structure of the tail fiber protein.
2. Pseudo-Domain Identification: The sequence is divided into pseudo-domains using a sigmoid distance pair (sDp) matrix, which groups residues with similar prediction confidence and spatial proximity .
3. Fraction Generation: Consecutive pseudo-domains are combined into fractions, with overlapping residues to facilitate superimposition.
4. Trimer Modeling: Each fraction is modeled as a trimer using AF2M.
5. Merging Fractions: Fractions are superimposed based on overlaps, paired, and connected to assemble the full fiber structure, followed by Amber relaxation for refinement .

Classification Results

Using this approach, 67 tail fibers were analyzed, resulting in:

• 16 distinct structural classes
• 89 domains These classes reveal patterns of modularity, convergence, divergence, and domain swapping, representing at least 24% of the known tail fiber universe . This classification provides insights into the evolution, functionality, and host specificity of phage tail fibers.

Functional Implications

Tail fibers attach to host receptors such as outer membrane proteins, exopolysaccharides, and flagella. The classification helps predict binding specificity and structural adaptations, which are critical for understanding phage-host interactions and designing phage-based applications .

Summary

The Tail Fiber Classification Code refers to the structural categorization of phage tail fibers into 16 classes and 89 domains using computational segmentation and modeling. RBPseg enables high-confidence structural predictions, providing a framework for studying the diversity and evolution of these essential viral proteins .