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 language | English |
|---|---|
| Pages (from-to) | 1404-1409 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 98 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 13 2001 |
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ASJC Scopus subject areas
- Genetics
- General
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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 journal › Article
}
TY - JOUR
T1 - Design of three-dimensional domain-swapped dimers and fibrous oligomers
AU - Ogihara, Nancy L.
AU - Ghirlanda, Giovanna
AU - Bryson, James W.
AU - Gingery, Mari
AU - DeGrado, William F.
AU - Eisenberg, David
PY - 2001/2/13
Y1 - 2001/2/13
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0035852764&partnerID=8YFLogxK
U2 - 10.1073/pnas.98.4.1404
DO - 10.1073/pnas.98.4.1404
M3 - Article
C2 - 11171963
AN - SCOPUS:0035852764
VL - 98
SP - 1404
EP - 1409
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 4
ER -