Article Metrics


Online attention

How coiled-coil assemblies accommodate multiple aromatic residues

DOI: 10.1021/acs.biomac.1c00131 DOI Help

Authors: Guto G. Rhys (University of Bristol; University of Bayreuth) , William M. Dawson (University of Bristol) , Joseph L. Beesley (University of Bristol) , Freddie J. O. Martin (University of Bristol) , R. Leo Brady (University of Bristol) , Andrew Thomson (University of Bristol; University of Glasgow) , Derek N. Woolfson (University of Bristol)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biomacromolecules , VOL 2

State: Published (Approved)
Published: April 2021
Diamond Proposal Number(s): 12342

Abstract: Rational protein design requires understanding the contribution of each amino acid to a targeted protein fold. For a subset of protein structures, namely, α-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 α 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 another more complex structure, the residues are buried and form an extended hydrogen-bond network.

Journal Keywords: Interfaces; Peptides and proteins; Crystal structure; Chemical structure; Aromatic compounds

Subject Areas: Chemistry, Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 26/04/2021 08:59

Discipline Tags:

Biochemistry Chemistry Structural biology Organic Chemistry Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)