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Updated: May 24, 2026
07:08
Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Rewiring of PDZ domain-ligand interaction network contributed to eukaryotic evolution
Jinho Kim1, Inhae Kim, Jae-Seong Yang
1Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Korea.
Plos Genetics
|February 21, 2012
Summary
PDZ domain interactions evolved significantly, with rewiring driving new protein functions, especially in nervous system development. This study maps the human PDZ interactome, revealing network expansion mechanisms.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Systems Biology
Background:
- PDZ domain-mediated interactions are crucial for signal transduction by assembling signaling components.
- The evolutionary history and molecular mechanisms of PDZ domain-ligand interactions remain largely unexplored.
Purpose of the Study:
- To construct the first comprehensive human PDZ domain-ligand interaction network (PDZNet).
- To investigate the evolutionary rewiring of PDZ domain-ligand interactions at a molecular level.
- To understand how interaction rewiring contributes to protein function evolution.
Main Methods:
- Construction of the human PDZNet including 1,213 interactions between 97 PDZ proteins and 591 ligands.
- Analysis of binding motif sequences and interaction strengths.
- Tracing evolutionary changes in C-terminal binding motifs of PDZ ligands.
Main Results:
- PDZNet connects 98% of human PDZ protein-mediated interactions into a single large network.
- Interaction rewiring through sequence mutation is a frequent evolutionary event, driving PDZNet expansion.
- Rewiring of PDZ interactions facilitated functional innovations, particularly in nervous system development.
Conclusions:
- PDZ domain-ligand interaction rewiring is a key mechanism for developing new protein functions.
- The study provides empirical support for network evolution models.
- PDZNet serves as a valuable resource for studying the PDZ-mediated signaling proteome.
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