ATP-independent control of autotransporter virulence protein transport via the folding properties of the secreted protein.
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 (ΔG(folding)) 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.
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556-5670, USA.
Jonathan P
JP
Renn
Mirco
M
Junker
Richard N
RN
Besingi
Esther
E
Braselmann
Patricia L
PL
Clark
D000255:Adenosine Triphosphate / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D008958:Models, Molecular; D017510:Protein Folding; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D010566:Virulence Factors, Bordetella; C068929:pertactin; D000255:Adenosine Triphosphate; D013762:Tetrahydrofolate Dehydrogenase