Design of three-dimensional domain-swapped dimers and fibrous oligomers

Nancy L. Ogihara, Giovanna Ghirlanda, James W. Bryson, Mari Gingery, William F. DeGrado, David Eisenberg

Research output: Contribution to journalArticlepeer-review

137 Citations (Scopus)


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 Å 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.

Original languageEnglish
Pages (from-to)1404-1409
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
Publication statusPublished - Feb 13 2001

ASJC Scopus subject areas

  • General

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