Structural highlights
Publication Abstract from PubMed
De novo protein design is advancing rapidly. However, most designs are for single states. Here we report a de novo designed peptide that forms multiple alpha-helical-bundle states that are accessible and interconvertible under the same conditions. Usually in such designs amphipathic alpha helices associate to form compact structures with consolidated hydrophobic cores. However, recent rational and computational designs have delivered open alpha-helical barrels with functionalisable cavities. By placing glycine judiciously in the helical interfaces of an alpha-helical barrel, we obtain both open and compact states in a single protein crystal. Molecular dynamics simulations indicate a free-energy landscape with multiple and interconverting states. Together, these findings suggest a frustrated system in which steric interactions that maintain the open barrel and the hydrophobic effect that drives complete collapse are traded-off. Indeed, addition of a hydrophobic co-solvent that can bind within the barrel affects the switch between the states both in silico and experimentally.
Structural resolution of switchable states of a de novo peptide assembly.,Dawson WM, Lang EJM, Rhys GG, Shelley KL, Williams C, Brady RL, Crump MP, Mulholland AJ, Woolfson DN Nat Commun. 2021 Mar 9;12(1):1530. doi: 10.1038/s41467-021-21851-8. PMID:33750792[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dawson WM, Lang EJM, Rhys GG, Shelley KL, Williams C, Brady RL, Crump MP, Mulholland AJ, Woolfson DN. Structural resolution of switchable states of a de novo peptide assembly. Nat Commun. 2021 Mar 9;12(1):1530. doi: 10.1038/s41467-021-21851-8. PMID:33750792 doi:http://dx.doi.org/10.1038/s41467-021-21851-8
