3D domain swapping: As domains continue to swap

Authors

  • Yanshun Liu,

    1. Howard Hughes Medical Institute, UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Department of Chemistry and Biochemistry and Biological Chemistry, University of California, Los Angeles, California 90095, USA
    Search for more papers by this author
  • David Eisenberg

    Corresponding author
    1. Howard Hughes Medical Institute, UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Department of Chemistry and Biochemistry and Biological Chemistry, University of California, Los Angeles, California 90095, USA
    • 201 Boyer Hall, P.O. Box 951570, Los Angeles, CA 90095-1570, USA; fax: (310) 206-3914.
    Search for more papers by this author

Abstract

Three-dimensional (3D) domain swapping creates a bond between two or more protein molecules as they exchange their identical domains. Since the term '3D domain swapping' was first used to describe the dimeric structure of diphtheria toxin, the database of domain-swapped proteins has greatly expanded. Analyses of the now about 40 structurally characterized cases of domain-swapped proteins reveal that most swapped domains are at either the N or C terminus and that the swapped domains are diverse in their primary and secondary structures. In addition to tabulating domain-swapped proteins, we describe in detail several examples of 3D domain swapping which show the swapping of more than one domain in a protein, the structural evidence for 3D domain swapping in amyloid proteins, and the flexibility of hinge loops. We also discuss the physiological relevance of 3D domain swapping and a possible mechanism for 3D domain swapping. The present state of knowledge leads us to suggest that 3D domain swapping can occur under appropriate conditions in any protein with an unconstrained terminus. As domains continue to swap, this review attempts not only a summary of the known domain-swapped proteins, but also a framework for understanding future findings of 3D domain swapping.

Ancillary