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Maintaining and breaking symmetry in homomeric coiled-coil assemblies

DOI: 10.1038/s41467-018-06391-y DOI Help

Authors: Guto G. Rhys (University of Bristol) , Christopher W. Wood (University of Bristol) , Eric J. M. Lang (University of Bristol) , Adrian J. Mulholland (University of Bristol) , R. Leo Brady (University of Bristol) , Andrew R. Thomson (University of Bristol) , Derek N. Woolfson (University of Bristol)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: October 2018
Diamond Proposal Number(s): 8922 , 12342

Open Access Open Access

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.

Subject Areas: Chemistry


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

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s41467-018-06391-y.pdf