Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein
Gruszka, Dominika T.
Farrance, Oliver E.
Fung, Herman K. H.
Jeffries, Cy M.
Svergun, Dmitri I.
Baumann, Christoph G.
Brockwell, David J.
Potts, Jennifer R.
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Gruszka, D. T., Whelan, F., Farrance, O. E., Fung, H. K. H., Paci, E., Jeffries, C. M., Svergun, D. I., et al. (2015). Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein. 6 (7271)https://doi.org/10.1038/ncomms8271
This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms8271
Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells. Such proteins need to project away from the bacterial surface and be resistant to significant mechanical force. SasG is a protein that forms extended fibrils on the surface of Staphylococcus aureus and promotes host adherence and biofilm formation. Here we show that, although monomeric and lacking covalent crosslinks, SasG maintains a highly extended conformation in solution. This extension is mediated through obligate folding cooperativity of the intrinsically disordered E domains that couple non-adjacent G5 domains thermodynamically, forming interfaces that are more stable than the domains themselves. Thus, counter-intuitively, the elongation of the protein appears to be dependent on the inherent instability of its domains. The remarkable mechanical strength of SasG arises from tandemly arrayed ‘clamp’ motifs within the folded domains. Our findings reveal an elegant minimal solution for the assembly of monomeric mechano-resistant tethers of variable length.
This research was supported by Biotechnology and Biological Research Council Grants BB/J006459/1 (D.T.G. and J.C.), BB/J005029/1 (F.W. and J.R.P), BB/G019452/1 (O.E.F and D.J.B) and BB/G020671/1 (C.G.B. and J.R.P.). H.K.H.F. is supported by a studentship from a Wellcome Trust 4-year PhD programme (WT095024MA). C.M.J. is supported by the German Federal Ministry of Education and Research (BMBF), grant BIOSCAT (contract N° 05K12YE1). J.C. is a Wellcome Trust Senior Research Fellow (WT/095195). J.R.P holds a British Heart Foundation Senior Basic Science Fellowship (FS/12/36/29588). The authors acknowledge the use of EMBL SAXS beamline P12 at Petra-3 (DESY, Hamburg, Germany) and Maxim Petoukhov (EMBL) for providing a modified version of SASR EF. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (grant agreement N°283570). The authors would like to thank Diamond Light Source for beamtime (proposal mx-7864) and Johan Turkenburg and Sam Hart for assistance with crystal testing and data collection.
External DOI: https://doi.org/10.1038/ncomms8271
This record's URL: http://www.repository.cam.ac.uk/handle/1810/248008
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/