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.
Highlights
Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells
Host cells and one another via specialized surface proteins, which need to project away from the bacterial surface and be resistant to mechanical stress[1,2]
The mechanisms commonly used by bacterial adhesins to achieve both extension and mechanical strength are multimeric assembly and/or covalent stabilization[1,3,4,5,6]
Summary
Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells. SasG is a protein that forms extended fibrils on the surface of Staphylococcus aureus and promotes host adherence and biofilm formation. We show that 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. Staphylococcal biofilms are clinically important functional micro-communities of bacteria[10] that cause hospital-acquired infections[11] and promote exchange of antibiotic resistance genes[12], presenting a significant global challenge Both SasG and accumulation-associated protein contain a central region with a variable (strain dependent) number of 128 amino acid repeats. Our study reveals the molecular basis for the efficient formation of elongated and mechanically resistant bacterial adhesins from a single polypeptide chain
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