Effective identification of bacterial type III secretion signals using joint element features

Area of Science:

• Microbiology
• Molecular Biology
• Bioinformatics

Background:

• The type III secretion system (T3SS) is crucial for bacterial virulence and host interactions, translocating effector proteins into host cells.
• The N-terminal sequences of these effectors dictate specific secretion, but the guiding mechanisms remain poorly understood.

Purpose of the Study:

• To investigate the N-terminal features (amino acid composition, secondary structure, solvent accessibility) that determine type III effector protein secretion.
• To develop a predictive model for identifying type III secreted proteins and explore their presence beyond typical bacterial pathogens.

Main Methods:

• Comparative analysis of N-terminal features between type III and non-type III secreted proteins.
• Development of a mathematical model integrating secondary structure and solvent accessibility for prediction.
• Genome-wide screening in Salmonella and experimental validation of predicted candidates.
• In silico and experimental prediction and validation in yeast.

Main Results:

• Secondary structure and solvent accessibility of N-termini are key features for specific type III secretion signal recognition.
• The 6th-10th amino acids in the N-terminus are particularly important for guiding specific secretion.
• A predictive model achieved high accuracy (∼96% sensitivity, ∼98% specificity) in identifying type III secreted proteins.
• Eight new Salmonella type III secreted protein candidates were validated, and secretion signals were found in yeast, with two yeast candidates experimentally confirmed.

Conclusions:

• Secondary structure and solvent accessibility provide crucial features for guiding specific type III secretion.
• The developed computational tool enables accurate in silico identification of novel type III secreted proteins.
• The findings suggest broader implications for understanding type III secretion specificity and the evolution of secreted proteins across different organisms, including eukaryotes.