Rational protein design requires understanding the contribution of each amino acid to a targeted protein fold. For a subset of protein structures, namely the -helical coiled coils (CCs), knowledge is sufficiently advanced to allow the rational de novo design of many structures, including entirely new protein folds. Current CC design rules center on using aliphatic hydrophobic residues predominantly to drive the folding and assembly of amphipathic helices. The consequences of using aromatic residues—which would be useful for introducing structural probes, and binding and catalytic functionalities—into these interfaces are not understood. There are specific examples of designed CCs containing such aromatic residues, e.g., phenylalanine-rich sequences, and the use of polar aromatic residues to make buried hydrogen-bond networks. However, it is not known generally if sequences rich in tyrosine can form CCs, or what CC assemblies these would lead to. Here we explore tyrosine-rich sequences in a general CC-forming background and resolve new CC structures. In one of these, an antiparallel tetramer, the tyrosine residues are solvent accessible and pack at the interface between the core and the surface. In the other more-complex structure, the residues are buried and form an extended hydrogen-bond network.
Bibliographical noteFunding Information:
G.G.R., J.L.B., A.R.T., W.M.D., and D.N.W. were supported by a European Research Council Advanced Grant (340764). G.G.R. and F.J.O.M. thank the Bristol Chemical Synthesis Centre for Doctoral Training funded by the Engineering and Physical Sciences Research Council (EP/G036764/1). D.N.W. held a Royal Society Wolfson Research Merit Award (WM140008).
© 2021 The Authors. Published by American Chemical Society.
- Bristol BioDesign Institute
- aromatic-aromatic interactions
- coiled coil
- de novo protein design
- peptide assembly
- pi-pi interactions