MotifAnalyzer-PDZ

MotifAnalyzer-PDZ analyzes and predicts PDZ domain interactions by filtering motif-satisfying C-terminal short linear motifs (SLiMs) across publicly available proteomes to identify candidate PDZ-binding proteins and evaluate their evolutionary conservation.

Key Features:

• Proteome filtering and comparison: Filters and compares motif-satisfying sequences from publicly available proteomes to identify candidate PDZ targets.
• C-terminal SLiM analysis: Analyzes SLiMs at the extreme C-terminus of proteins that mediate PDZ domain binding.
• Evolutionary conservation assessment: Examines evolutionary sequence conservation of motif-satisfying sequences across species.
• Positional amino acid enrichment: Calculates and compares positional amino acid enrichments in PDZ motif-satisfying sequences across over a dozen organisms.
• Cross-species target identification: Identifies candidate targets across species, including three C-terminal sequences in choanoflagellates that bind the Monsiga brevicollis SHANK1 PDZ domain (mbSHANK1) with endogenously-relevant affinities.
• Prediction validation: Supports predictions that have been validated by biochemical testing of novel human PDZ targets.
• Generalizable to other SLiM-binding domains: Enables similar analyses for other SLiM-binding domains, such as kinase motifs.

Scientific Applications:

• Evolution of PDZ-binding specificity: Investigates the evolution of PDZ-binding target specificity across organisms.
• Identification of biologically relevant interactions: Predicts and prioritizes biologically relevant PDZ interactions, including targets related to cytosolic and receptor tyrosine kinases.
• Cross-species comparative studies: Compares PDZ motif usage and enrichment patterns across multiple organisms, including humans and choanoflagellates.
• Prioritization for experimental validation: Ranks candidate PDZ targets for follow-up biochemical testing.
• Extension to other motif systems: Applies the same analytical approach to other SLiM-mediated interactions, such as kinase recognition motifs.

Methodology:

Filtering and comparing motif-satisfying sequences from publicly available proteomes, examining evolutionary sequence conservation, and calculating positional amino acid enrichments in PDZ motif-satisfying sequences across organisms.