Structural and functional aspects of domain motions in proteins

Three distinct categories of large-scale flexibility in proteins have been documented by single-crystal X-ray diffraction studies: the relatively free movement of essentially rigid globular domains that are connected by a flexible segment of polypeptide, the reorientation of essentially rigid domains among a few distinct conformations, and the concerted transition of a contiguous region of the surface of a protein from a disordered state to an ordered state. In a number of examples, well-defined functions can be assigned to these large-scale structural changes. The occurrence of such motions in proteins of known structure is reviewed, and the best-studied examples are discussed in detail to allow a critical evaluation of the methods used to identify and study these motions.