In coiled-coil, CC, protein structures α-helices wrap around one another to form rope-like assemblies. Most natural and designed CCs have two–four helices and cyclic, Cn, or dihedral, Dn, symmetry. Increasingly, CCs with five or more helices are being reported.
A subset of these higher-order CCs is of interest as they have accessible central channels that can be functionalised. They are α-helical barrels. These extended cavities are surprising given the drive to maximise buried hydrophobic surfaces during protein folding and assembly in water.
Published in Nature Communications, scientists in Derek Woolfson's lab at the University of Bristol, show that α-helical barrels can be maintained by the strategic placement of β-branched aliphatic residues lining the lumen. Otherwise, the structures collapse or adjust to give more-complex multi-helix assemblies without Cn or Dn symmetry.
Nonetheless, the structural hallmark of CCs—namely, knobs-into-holes packing of side chains between helices, is maintained leading to classes of CCs hitherto unobserved in nature or accessed by design.
Maintaining and Breaking Symmetry in Homomeric Coiled-Coil Assemblies
Guto G. Rhys, Christopher W. Wood, Eric J.M. Lang, Adrian J. Mulholland, R. Leo Brady, Andrew R. Thomson, and Derek N. Woolfson
NATURE COMMUNICATIONS, 2018, 9:4132, DOI: 10.1038/s41467-018-06391-y