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Publication - Professor Dek Woolfson

    Maintaining and breaking symmetry in homomeric coiled-coil assemblies

    Citation

    Rhys, G, Wood, CW, Lang, EJM, Mulholland, A, Brady, RL, Thomson, A & Woolfson, D, 2018, ‘Maintaining and breaking symmetry in homomeric coiled-coil assemblies’. Nature Communications, vol 9.

    Abstract

    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. Here, we 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.

    Full details in the University publications repository