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De novo design of a non-local β-sheet protein with high stability and accuracy
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October 29 2018
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Source: Nat Struct Mol Biol. 25(11):1028-1034
[PDF-889.31 KB]
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Alternative Title:Nat Struct Mol Biol
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Description:β-sheet proteins carry out critical functions in biology, and hence are attractive scaffolds for computational protein design. Despite this potential, de novo design of all-β-sheet proteins from first principles lags far behind the design of all-α or mixed-αβ domains owing to their non-local nature and the tendency of exposed β-strand edges to aggregate. Through study of loops connecting unpaired β-strands (β-arches), we have identified a series of structural relationships between loop geometry, side chain directionality and β-strand length that arise from hydrogen bonding and packing constraints on regular β-sheet structures. We use these rules to de novo design jellyroll structures with double-stranded β-helices formed by eight antiparallel β-strands. The nuclear magnetic resonance structure of a hyperthermostable design closely matched the computational model, demonstrating accurate control over the β-sheet structure and loop geometry. Our results open the door to the design of a broad range of non-local β-sheet protein structures.
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Pubmed ID:30374087
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Pubmed Central ID:PMC6219906
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Volume:25
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Issue:11
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