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 journalArticle

133 Citations (Scopus)

Abstract

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
Volume98
Issue number4
DOIs
Publication statusPublished - Feb 13 2001

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Crystallography
Biocompatible Materials
Electron Microscopy
Proteins
X-Rays
Protein Domains
Dynamic Light Scattering

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Design of three-dimensional domain-swapped dimers and fibrous oligomers. / Ogihara, Nancy L.; Ghirlanda, Giovanna; Bryson, James W.; Gingery, Mari; DeGrado, William F.; Eisenberg, David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 4, 13.02.2001, p. 1404-1409.

Research output: Contribution to journalArticle

Ogihara, Nancy L. ; Ghirlanda, Giovanna ; Bryson, James W. ; Gingery, Mari ; DeGrado, William F. ; Eisenberg, David. / Design of three-dimensional domain-swapped dimers and fibrous oligomers. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 4. pp. 1404-1409.
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