The PDZ Domain as a Complex Adaptive System

摘要: Specific protein associations define the wiring of interaction networks and thus control organization functioning cell as a whole. Peptide recognition by PDZ other domains represents one best-studied classes specific associations. However, mechanistic understanding relationship between selectivity promiscuity commonly observed in interactions mediated peptide modules well its functional meaning remain elusive. To address these questions comprehensive manner, two large populations artificial natural ligands six archetypal from synaptic proteins PSD95 SAP97 were generated target-assisted iterative screening (TAIS) combinatorial libraries synthesis proteomic fragments, correspondingly. A comparative statistical analysis affinity-ranked yielded picture known novel ligand specificity determinants, revealing hitherto unappreciated combination adaptive plasticity inherent to domain recognition. We propose reconceptualization terms complex system representing flexible compromise rigid order exquisite chaos unselective promiscuity, which has evolved mediate mutually contradictory properties required such higher sub-cellular organizations synapses, junctions, others – organizational structure plasticity/adaptability. The generalization this regard is consistent with image macromolecular opposed clockwork.