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Maintaining and breaking symmetry in homomeric coiled-coil assemblies.

ABSTRACT: In coiled-coil (CC) protein structures ?-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 ?-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 ?-helical barrels can be maintained by the strategic placement of ?-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.

SUBMITTER: Rhys GG

PROVIDER: S-EPMC6175849 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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