Design of three-dimensional domain-swapped dimers and fibrous oligomers.
Three-dimensional (3D) domain-swapped proteins are intermolecularly folded analogs of monomeric proteins; both are stabilized by the identical interactions, but the individual domains interact intramolecularly in monomeric proteins, whereas they form intermolecular interactions in 3D domain-swapped structures. The structures and conditions of formation of several domain-swapped dimers and trimers are known, but the formation of higher order 3D domain-swapped oligomers has been less thoroughly studied. Here we contrast the structural consequences of domain swapping from two designed three-helix bundles: one with an up-down-up topology, and the other with an up-down-down topology. The up-down-up topology gives rise to a domain-swapped dimer whose structure has been determined to 1.5 A resolution by x-ray crystallography. In contrast, the domain-swapped protein with an up-down-down topology forms fibrils as shown by electron microscopy and dynamic light scattering. This demonstrates that design principles can predict the oligomeric state of 3D domain-swapped molecules, which should aid in the design of domain-swapped proteins and biomaterials.
Ogihara
N L
NL
UCLA-DOE Laboratory of Structural Biology and the Department of Chemistry and Biochemistry, P.O. Box 951570, University of California, Los Angeles, CA 90095-1570, USA.
Ghirlanda
G
G
Bryson
J W
JW
Gingery
M
M
DeGrado
W F
WF
Eisenberg
D
D
D019281:Dimerization; D009842:Oligopeptides / Q000737:chemistry*; D017510:Protein Folding; D017434:Protein Structure, Tertiary
D009842:Oligopeptides