ATP-Independent Control of Autotransporter Virulence Protein Transport via the Folding Properties of the Secreted Protein

• Published in: Chemistry & biology Vol. 19; no. 2; pp. 287 - 296
• Main Authors: Renn, Jonathan P., Junker, Mirco, Besingi, Richard N., Braselmann, Esther, Clark, Patricia L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 24.02.2012
• Subjects: Adenosine Triphosphate - metabolism; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - metabolism; Bacterial Outer Membrane Proteins - secretion; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Bacterial Proteins - secretion; Gram-Negative Bacteria - metabolism; Models, Molecular; Protein Folding; Protein Stability; Protein Structure, Tertiary; Protein Transport; Tetrahydrofolate Dehydrogenase - chemistry; Tetrahydrofolate Dehydrogenase - metabolism; Virulence Factors, Bordetella - chemistry; Virulence Factors, Bordetella - metabolism
• ISSN: 1074-5521; 1879-1301
• DOI: 10.1016/j.chembiol.2011.11.009

Autotransporter (AT) proteins are the largest class of extracellular virulence proteins secreted from Gram-negative bacteria. The mechanism by which AT proteins cross the bacterial outer membrane (OM), in the absence of ATP or another external energy source, is unknown. Here we demonstrate a linear correlation between localized regions of stability (ΔGfolding) in the mature virulence protein (the AT “passenger”) and OM secretion efficiency. Destabilizing the C-terminal β-helical domain of a passenger reduced secretion efficiency. In contrast, destabilizing the globular N-terminal domain of a passenger produced a linearly correlated increase in secretion efficiency. Thus, C-terminal passenger stability facilitates OM secretion, whereas N-terminal stability hinders it. The contributions of regional passenger stability to OM secretion demonstrate a crucial role for the passenger itself in directing its secretion, suggesting a novel type of ATP-independent, folding-driven transporter. [Display omitted] ► Protein stability at N and C termini have opposing effects on autotransporter secretion ► Highly secreted proteins are less stable at N terminus, more stable at C terminus ► Unexpected correlation between equilibrium state function and biological mechanism ► Suggests novel folding-driven mechanism for ATP-independent protein secretion