Three-dimensional domain swapping in the protein structure space.

Since the proposal of three-dimensional (3D) domain swapping, many 3D domain-swapped structures have been reported. However, when compared with the vast protein structure space, it is still unclear whether 3D domain swapping is a general mechanism for protein assembly. Here, we investigated this possibility by constructing a dataset consisting of more than 500 domain-swapped structures. The domain-swapped structures were mapped into the protein structure space. We found that about 10% of protein folds and 5% of protein families contain domain-swapped structures. When comparing the domain-swapped structures in a family/superfamily, we found that proteins within a family/superfamily can swap in different ways. Interface analysis revealed that the hinge loops contributed more than half of the open interface in 70% of bona fide domain-swapped dimers, indicating that the hinge loops play an important role in stabilizing the domain-swapped conformations. Our study supports the suggestion that domain swapping is a general property of all proteins and will facilitate further understanding the mechanism of 3D domain swapping.