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3D domain swapping: as domains continue to swap
1Howard 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.
Summary
Three-dimensional (3D) domain swapping is a protein dimerization process where identical domains are exchanged. This review summarizes known cases and suggests 3D domain swapping may occur in any protein with an unconstrained terminus.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Science
Background:
- Three-dimensional (3D) domain swapping involves the exchange of identical protein domains between molecules.
- First observed in diphtheria toxin, the phenomenon is now documented in numerous proteins.
Purpose of the Study:
- To review and analyze structurally characterized cases of 3D domain swapping.
- To provide a framework for understanding future discoveries in protein domain swapping.
Main Methods:
- Database compilation of known domain-swapped proteins.
- Structural analysis of protein structures exhibiting domain swapping.
- Review of existing literature on 3D domain swapping.
Main Results:
- Approximately 40 cases of 3D domain-swapped proteins have been structurally characterized.
- Swapped domains are typically located at the N or C termini and exhibit diverse structures.
- Examples include multi-domain swapping, amyloid protein involvement, and hinge loop flexibility.
Conclusions:
- 3D domain swapping is a significant protein structural mechanism.
- The process can potentially occur in any protein with an unconstrained terminus under suitable conditions.
- This review serves as a comprehensive summary and a guide for future research.