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Implications of 3D Domain Swapping for Protein Folding, Misfolding and Function

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Protein Dimerization and Oligomerization in Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 747))

Abstract

Three-dimensional domain swapping is the process by which two identical protein chains exchange a part of their structure to form an intertwined dimer or higher-order oligomer. The phenomenon has been observed in the crystal structures of a range of different proteins. In this chapter we review the experiments that have been performed in order to understand the sequence and structural determinants of domain-swapping and these show how the general principles obtained can be used to engineer proteins to domain swap. We discuss the role of domain swapping in regulating protein function and as one possible mechanism of protein misfolding that can lead to aggregation and disease. We also review a number of interesting pathways of macromolecular assembly involving β-strand insertion or complementation that are related to the domain-swapping phenomenon.

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Authors and Affiliations

  1. VIB Switch Laboratory, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Leuven, Belgium

    Frederic Rousseau & Joost Schymkowitz

  2. Department of Chemistry, University of Cambridge, Cambridge, UK

    Laura S. Itzhaki

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  1. Frederic Rousseau
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  2. Joost Schymkowitz
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  3. Laura S. Itzhaki
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Correspondence to Laura S. Itzhaki .

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  1. School of Molecular Bioscience, University of Sydney, Sydney, Australia

    Jacqueline M. Matthews PhD

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Rousseau, F., Schymkowitz, J., Itzhaki, L.S. (2012). Implications of 3D Domain Swapping for Protein Folding, Misfolding and Function. In: Matthews, J.M. (eds) Protein Dimerization and Oligomerization in Biology. Advances in Experimental Medicine and Biology, vol 747. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3229-6_9

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