title: Domain swapping is a consequence of minimal frustration.
abstract: The same energy landscape principles associated with the folding of proteins into their monomeric conformations should also describe how these proteins oligomerize into domain-swapped conformations. We tested this hypothesis by using a simplified model for the epidermal growth factor receptor pathway substrate 8 src homology 3 domain protein, both of whose monomeric and domain-swapped structures have been solved. The model, which we call the symmetrized Gō-type model, incorporates only information regarding the monomeric conformation in an energy function for the dimer to predict the domain-swapped conformation. A striking preference for the correct domain-swapped structure was observed, indicating that overall monomer topology is a main determinant of the structure of domain-swapped dimers. Furthermore, we explore the free energy surface for domain swapping by using our model to characterize the mechanism of oligomerization.
authors.affiliation: Center for Theoretical Biological Physics and Department of Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Sichun
authors.initials: S
authors.lastname: Yang
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Cho
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Levy
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Cheung
authors.forename: Herbert
authors.initials: H
authors.lastname: Levine
authors.forename: Peter G
authors.initials: PG
authors.lastname: Wolynes
authors.forename: José N
authors.initials: JN
authors.lastname: Onuchic
mesh_terms: D001665:Binding Sites; D008962:Models, Theoretical; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins