Maintaining and breaking symmetry in homomeric coiled-coil assemblies

Rhys, G. G., Wood, C. W., Lang, E. J.M., Mulholland, A. J., Brady, R. L., Thomson, A. R. and Woolfson, D. N. (2018) Maintaining and breaking symmetry in homomeric coiled-coil assemblies. Nature Communications, 9(1), 4132. (doi:10.1038/s41467-018-06391-y) (PMID:30297707) (PMCID:PMC6175849)

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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 (C ) or dihedral (D ) 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 C or D 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.

Item Type:Articles
Additional Information:G.G.R. thanks the Bristol Chemical Synthesis Centre for Doctoral Training funded by the British taxpayer via the Engineering and Physical Sciences Research Council (EP/G036764/1). G.G.R., C.W.W., A.R.T. and D.N.W. are supported by the European Research Council (340764). D.N.W., E.J.M.L. and A.J.M. are supported by the BBSRC and EPSRC through the BrisSynBio Synthetic Biology Research Centre (BB/L01386X1). A.J.M. is supported by EPSRC grant number EP/M022609/1. D.N.W. holds a Royal Society Wolfson Research Merit Award. We thank the University of Bristol School of Chemistry Mass Spectrometry Facility for access to the EPSRC-funded Bruker Ultraflex MALDI-TOF/TOF instrument (EP/K03927X/1), and BrisSynBio for access to a plate reader (BB/L01386X/1).
Glasgow Author(s) Enlighten ID:Thomson, Dr Drew
Authors: Rhys, G. G., Wood, C. W., Lang, E. J.M., Mulholland, A. J., Brady, R. L., Thomson, A. R., and Woolfson, D. N.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9(1):4132
Publisher Policy:Reproduced under a Creative Commons License

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