SHARK-capture identifies functional motifs in intrinsically disordered protein regions

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• Intrinsically disordered regions (IDRs) play crucial roles in cellular functions.
• Detecting sequence motifs in IDRs is challenging due to their rapid evolution and lack of stable structure.
• Existing alignment-based tools are limited for motif discovery in IDRs.

Purpose of the Study:

• To develop a novel, alignment-free computational tool for systematic motif detection in intrinsically disordered regions (IDRs).
• To improve the accuracy and reliability of motif identification in challenging, rapidly evolving protein sequences.
• To provide a valuable resource for researchers studying protein function and evolution.

Main Methods:

• Developed SHARK-capture, an alignment-free motif detection tool.
• Incorporated amino acid physicochemical properties to assess motif similarity flexibly.
• Validated performance through systematic benchmarking and identification of known functional motifs.

Main Results:

• SHARK-capture demonstrates consistently strong performance and superior residue-level accuracy in motif detection.
• Successfully identified known functional motifs in BuGZ protein orthologs.
• Discovered and experimentally verified a novel motif in yeast Ded1p IDR that enhances ATPase activity.
• Generated a comprehensive resource of 10,889 motifs across 2695 yeast IDRs.

Conclusions:

• SHARK-capture is a precise and effective tool for systematic identification of conserved regions in IDRs.
• The tool overcomes limitations of alignment-based methods for motif discovery in disordered protein regions.
• The generated motif resource and the SHARK-capture tool are valuable assets for biological research.