De novo design of a non-local β-sheet protein with high stability and accuracy
| Autor: | Gustav Oberdorfer, Santrupti Nerli, David Baker, Lauren Carter, Konstantinos Tripsianes, Nikolaos G. Sgourakis, Andrew C. McShan, Lucas G. Nivón, Enrique Marcos, Tamuka M. Chidyausiku, Audrey Davis, Thomas Evangelidis |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Folding Protein Conformation Protein design Beta sheet 010402 general chemistry Antiparallel (biochemistry) Topology Protein Engineering 01 natural sciences Article 03 medical and health sciences Protein structure Structural Biology Directionality Computer Simulation Amino Acid Sequence Molecular Biology Protein secondary structure Nuclear Magnetic Resonance Biomolecular Protein Stability Proteins Hydrogen Bonding Non local 0104 chemical sciences 030104 developmental biology Protein folding Protein Conformation beta-Strand |
| Zdroj: | Nature structural & molecular biology |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | 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. Baker, Marcos and colleagues analyze β-arches (loops connecting unpaired β-strands) and derive rules used for de novo design of a hyperthermostable jellyroll structure, with eight antiparallel β-strands forming double-stranded β-helices. |
| Databáze: | OpenAIRE |
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