Structural highlights
Publication Abstract from PubMedbeta-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-beta-sheet proteins from first principles lags far behind the design of all-alpha or mixed-alphabeta domains owing to their non-local nature and the tendency of exposed beta-strand edges to aggregate. Through study of loops connecting unpaired beta-strands (beta-arches), we have identified a series of structural relationships between loop geometry, side chain directionality and beta-strand length that arise from hydrogen bonding and packing constraints on regular beta-sheet structures. We use these rules to de novo design jellyroll structures with double-stranded beta-helices formed by eight antiparallel beta-strands. The nuclear magnetic resonance structure of a hyperthermostable design closely matched the computational model, demonstrating accurate control over the beta-sheet structure and loop geometry. Our results open the door to the design of a broad range of non-local beta-sheet protein structures. De novo design of a non-local beta-sheet protein with high stability and accuracy.,Marcos E, Chidyausiku TM, McShan AC, Evangelidis T, Nerli S, Carter L, Nivon LG, Davis A, Oberdorfer G, Tripsianes K, Sgourakis NG, Baker D Nat Struct Mol Biol. 2018 Nov;25(11):1028-1034. doi: 10.1038/s41594-018-0141-6., Epub 2018 Oct 29. PMID:30374087[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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