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Elife. 2015 Dec 9;4. pii: e11012. doi: 10.7554/eLife.11012.

Precise assembly of complex beta sheet topologies from de novo designed building blocks.

Author information

1
Institute for Protein Design, University of Washington, Seattle, United States.
2
Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
3
Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, United States.
4
Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway, 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.

KEYWORDS:

E. coli; beta sheets; biophysics; computational biology; protein design; protein folding; structural biology; systems biology

PMID:
26650357
PMCID:
PMC4737653
DOI:
10.7554/eLife.11012
[Indexed for MEDLINE]
Free PMC Article

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