title: Implications of 3D domain swapping for protein folding, misfolding and function.
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.
authors.affiliation: VIB Switch Laboratory, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Rousseau
authors.forename: Joost
authors.initials: J
authors.lastname: Schymkowitz
authors.forename: Laura S
authors.initials: LS
authors.lastname: Itzhaki
mesh_terms: D000818:Animals; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000502:physiology; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D057165:Proteostasis Deficiencies / Q000378:metabolism; D013329:Structure-Activity Relationship; D014780:Viruses
chemical_list: D021122:Protein Subunits; D011506:Proteins