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, 4132. (doi: 10.1038/s41467-018-06391-y) (PMID:30297707) (PMCID:PMC6175849)
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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 (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 |
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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). |
Status: | Published |
Refereed: | Yes |
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 Research |
ISSN: | 2041-1723 |
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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