Precise assembly of complex beta sheet topologies from de novo designed building blocks
- University of Washington, United States
- Fred Hutchinson Cancer Research Center, United States
- Columbia University, United States
- Rutgers, The State University of New Jersey, United States
Abstract
Design of complex alpha-beta protein topologies poses a challenge because of the large number of alternative packing arrangements. A similar challenge presumably limited the emergence of large and complex protein topologies in evolution. Here we demonstrate that protein topologies with six and seven-stranded beta sheets can be designed by insertion of one de novo designed beta sheet containing protein into another such that the two beta sheets are merged to form a single extended sheet, followed by amino acid sequence optimization at the newly formed strand-strand, strand-helix, and helix-helix interfaces. Crystal structures of two such designs closely match the computational design models. Searches for similar structures in the SCOP protein domain database yield only weak matches with different beta sheet connectivities. A similar beta sheet fusion mechanism may have contributed to the emergence of complex beta sheets during natural protein evolution.
Article and author information
Author details
Reviewing Editor
- Nir Ben-Tal, Tel Aviv University, Israel
Version history
- Received: August 20, 2015
- Accepted: December 8, 2015
- Accepted Manuscript published: December 9, 2015 (version 1)
- Version of Record published: January 20, 2016 (version 2)
Copyright
© 2015, King et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Precise assembly of complex beta sheet topologies from de novo designed building blocks
eLife 4:e11012.
https://doi.org/10.7554/eLife.11012
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