Some (dis)assembly required: partial unfolding in the Par-6 allosteric switch

摘要: Allostery is commonly described as a functional connection between two distant sites in protein, where binding event at one site alters affinity the other. Here we review conformational dynamics that encode an allosteric switch PDZ domain of Par-6. Par-6 scaffold protein organizes other proteins into complex required to initiate and maintain cell polarity. NMR measurements revealed samples evolutionarily conserved unfolding intermediate allowing rearrangement adjacent loop residues control ligand affinity. Cdc42 creates novel interface adjoining CRIB motif stabilizes high-affinity conformation. Thermodynamic kinetic studies suggest partial integral part switching mechanism. The CRIB-PDZ module illustrates important structural aspects evolution: domains same can give rise regulation, thermodynamic stability may be sacrificed increase sampling frequency for switching.