Tandem Domains with Tuned Interactions Are a Powerful Biological Design Principle.

• Main Authors: Ruth Nussinov, Chung-Jung Tsai
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2015-01-01
• Series: PLoS Biology
• Online Access: http://europepmc.org/articles/PMC4664463?pdf=render

Allosteric effects of mutations, ligand binding, or post-translational modifications on protein function occur through changes to the protein's shape, or conformation. In a cell, there are many copies of the same protein, all experiencing these perturbations in a dynamic fashion and fluctuating through different conformations and activity states. According to the "conformational selection and population shift" theory, ligand binding selects a particular conformation. This perturbs the ensemble and induces a population shift. In a new PLOS Biology paper, Melacini and colleagues describe a novel model of protein regulation, the "Double-Conformational Selection Model", which demonstrates how two tandem ligand-binding domains interact to regulate protein function. Here we explain how tandem domains with tuned interactions-but not single domains-can provide a blueprint for sensitive activation sensors within a narrow window of ligand concentration, thereby promoting signaling control.