Domain swapping is a consequence of minimal frustration.
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.
Yang
Sichun
S
Center for Theoretical Biological Physics and Department of Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cho
Samuel S
SS
Levy
Yaakov
Y
Cheung
Margaret S
MS
Levine
Herbert
H
Wolynes
Peter G
PG
Onuchic
José N
JN
D001665:Binding Sites; D008962:Models, Theoretical; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D011506:Proteins