title: Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein.
abstract: Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells. Such proteins need to project away from the bacterial surface and resist significant mechanical forces. 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 cross-links, 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, counterintuitively, 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.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Dominika T
authors.initials: DT
authors.lastname: Gruszka
authors.affiliation: Department of Biology, University of York, Wentworth Way, York YO10 5DD, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Whelan
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Farrance
authors.affiliation: Department of Biology, University of York, Wentworth Way, York YO10 5DD, UK.
authors.forename: Herman K H
authors.initials: HK
authors.lastname: Fung
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Paci
authors.affiliation: European Molecular Biology Laboratory, Hamburg Unit, Notkestrasse 85, 22603 Hamburg, Germany.
authors.forename: Cy M
authors.initials: CM
authors.lastname: Jeffries
authors.affiliation: European Molecular Biology Laboratory, Hamburg Unit, Notkestrasse 85, 22603 Hamburg, Germany.
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.affiliation: Faculty of Life Sciences, Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Michael Smith Building, Greater Manchester M13 9PT, UK.
authors.forename: Clair
authors.initials: C
authors.lastname: Baldock
authors.affiliation: Department of Biology, University of York, Wentworth Way, York YO10 5DD, UK.
authors.forename: Christoph G
authors.identifier: 000000028818972X
authors.initials: CG
authors.lastname: Baumann
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brockwell
authors.affiliation: Department of Biology, University of York, Wentworth Way, York YO10 5DD, UK.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Potts
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Clarke
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry*; D018441:Biofilms; D018360:Crystallography, X-Ray; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013211:Staphylococcus aureus; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D064267:Intrinsically Disordered Proteins; D008565:Membrane Proteins; C524374:SasG protein, Staphylococcus aureus