Observation of signal transduction in three-dimensional domain swapping

p13(suc1) (suc1) has two native states, a monomer and a domain-swapped dime r. The structure of each subunit in the dimer is identical to that of the m onomer, except for the hinge loop that connects the exchanging domains. Her e we find that single point mutations at sites throughout the protein and l igand binding both shift the position of the equilibrium between monomer an d dimer. The hinge loop was shown previously to act as a loaded molecular s pring that releases tension present in the monomer by adopting an alternati ve conformation in the dimer. The results here indicate that the release of strain propagates throughout the entire protein and alters the energetics of regions remote from the hinge. Our data illustrate how the signal confer red by the conformational change of a protein loop, elicited by domain swap ping, ligand binding or mutation, can be sensed by a distant active site. T his work highlights the potential role of strained loops in proteins: the e nergy they store can be used for both signal transduction and allostery, an d they could steer the evolution of protein function. Finally, a structural mechanism for the role of suc1 as an adapter molecule is proposed.