Exploring the repeat protein universe through computational protein design [electronic resource].
- Washington, D.C. : United States. Dept. of Energy. Office of Basic Energy Sciences, 2015.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
- Physical Description:
- pages 580-584 : digital, PDF file
- Additional Creators:
- Lawrence Berkeley National Laboratory
United States. Department of Energy. Office of Basic Energy Sciences
National Science Foundation (U.S.)
United States. Defense Threat Reduction Agency
United States. Air Force. Office of Scientific Research
National Institutes of Health (U.S.)
United States. Department of Energy. Office of Scientific and Technical Information
- A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. In this paper, we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix–loop–helix–loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Finally, our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.
- Published through SciTech Connect.
Nature (London) 528 7583 ISSN 0028-0836 AM
TJ Brunette; Fabio Parmeggiani; Po-Ssu Huang; Gira Bhabha; Damian C. Ekiert; Susan E. Tsutakawa; Greg L. Hura; John A. Tainer; David Baker.
Howard Hughes Medical Inst. (HHMI) (United States)
Damon Runyon Cancer Research Foundation (United States)
Human Frontier Science Program (HFSP) (France)
- Funding Information:
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