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PDBsum entry 6e5c
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De novo protein
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PDB id
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6e5c
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References listed in PDB file
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Key reference
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Title
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De novo design of a non-Local β-Sheet protein with high stability and accuracy.
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Authors
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E.Marcos,
T.M.Chidyausiku,
A.C.Mcshan,
T.Evangelidis,
S.Nerli,
L.Carter,
L.G.Nivón,
A.Davis,
G.Oberdorfer,
K.Tripsianes,
N.G.Sgourakis,
D.Baker.
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Ref.
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Nat Struct Mol Biol, 2018,
25,
1028-1034.
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PubMed id
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Abstract
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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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