De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity
Abstract
In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks.We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen-bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen-bond networks with atomic accuracy enables the programming of protein interaction specificity for a broad range of synthetic biology applications; more generally, our results demonstrate that, even with the tremendous diversity observed in nature, there are fundamentally new modes of interaction to be discovered in proteins.
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1355858
- Alternate Identifier(s):
- OSTI ID: 1530239
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- Science
- Additional Journal Information:
- Journal Name: Science Journal Volume: 352 Journal Issue: 6286; Journal ID: ISSN 0036-8075
- Publisher:
- American Association for the Advancement of Science (AAAS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Boyken, S. E., Chen, Z., Groves, B., Langan, R. A., Oberdorfer, G., Ford, A., Gilmore, J. M., Xu, C., DiMaio, F., Pereira, J. H., Sankaran, B., Seelig, G., Zwart, P. H., and Baker, D. De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity. United States: N. p., 2016.
Web. doi:10.1126/science.aad8865.
Boyken, S. E., Chen, Z., Groves, B., Langan, R. A., Oberdorfer, G., Ford, A., Gilmore, J. M., Xu, C., DiMaio, F., Pereira, J. H., Sankaran, B., Seelig, G., Zwart, P. H., & Baker, D. De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity. United States. https://doi.org/10.1126/science.aad8865
Boyken, S. E., Chen, Z., Groves, B., Langan, R. A., Oberdorfer, G., Ford, A., Gilmore, J. M., Xu, C., DiMaio, F., Pereira, J. H., Sankaran, B., Seelig, G., Zwart, P. H., and Baker, D. Thu .
"De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity". United States. https://doi.org/10.1126/science.aad8865.
@article{osti_1355858,
title = {De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity},
author = {Boyken, S. E. and Chen, Z. and Groves, B. and Langan, R. A. and Oberdorfer, G. and Ford, A. and Gilmore, J. M. and Xu, C. and DiMaio, F. and Pereira, J. H. and Sankaran, B. and Seelig, G. and Zwart, P. H. and Baker, D.},
abstractNote = {In nature, structural specificity in DNA and proteins is encoded differently: In DNA, specificity arises from modular hydrogen bonds in the core of the double helix, whereas in proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Here, we describe a general approach for designing a wide range of protein homo-oligomers with specificity determined by modular arrays of central hydrogen-bond networks.We use the approach to design dimers, trimers, and tetramers consisting of two concentric rings of helices, including previously not seen triangular, square, and supercoiled topologies. X-ray crystallography confirms that the structures overall, and the hydrogen-bond networks in particular, are nearly identical to the design models, and the networks confer interaction specificity in vivo. The ability to design extensive hydrogen-bond networks with atomic accuracy enables the programming of protein interaction specificity for a broad range of synthetic biology applications; more generally, our results demonstrate that, even with the tremendous diversity observed in nature, there are fundamentally new modes of interaction to be discovered in proteins.},
doi = {10.1126/science.aad8865},
journal = {Science},
number = 6286,
volume = 352,
place = {United States},
year = {Thu May 05 00:00:00 EDT 2016},
month = {Thu May 05 00:00:00 EDT 2016}
}
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