Domain Analysis and Motif Matcher (DAMM): A Program to Predict Selectivity Determinants in Monosiga brevicollis PDZ...

Area of Science:

• Evolutionary biology
• Molecular biology
• Biochemistry

Background:

• Choanoflagellates are unicellular eukaryotes, evolutionarily linked to metazoans, exhibiting complex signaling pathways.
• They possess numerous PDZ domains, key peptide-binding modules involved in diverse cellular functions across all domains of life.
• Understanding choanoflagellate PDZ domain function may illuminate the evolutionary origins of multicellularity.

Purpose of the Study:

• To develop a computational tool for analyzing PDZ domain specificity in choanoflagellates.
• To characterize the target specificity of a specific PDZ domain-containing protein from *Monosiga brevicollis* (A9UPE9_MONBE).
• To investigate the evolutionary implications of PDZ domain signaling in the context of metazoan origins.

Main Methods:

• Development of the Domain Analysis and Motif Matcher (DAMM) computational software.
• Comparative analysis of PDZ domain sequence identity with human PDZ domains.
• Protein biochemistry, fluorescence polarization, and structural analyses to determine binding affinities and specificities.
• Literature searches for known human PDZ-interacting sequences.

Main Results:

• The DAMM software was developed to predict PDZ domain target specificity.
• The *M. brevicollis* PDZ domain A9UPE9_MONBE shows similarity to the human DLG family of PDZ domains.
• Two endogenous peptide ligands were identified that bind A9UPE9_MONBE PDZ with high affinity (<100 μM).

Conclusions:

• The developed computational approach enables prediction of PDZ domain targets in choanoflagellates and other organisms.
• Characterization of A9UPE9_MONBE provides insights into choanoflagellate signaling pathways.
• This research contributes to understanding the role of PDZ domains in the evolution of multicellularity and metazoan development.