title: An alternative outer membrane secretion mechanism for an autotransporter protein lacking a C-terminal stable core.
abstract: Autotransporter (AT) proteins are a broad class of virulence factors from Gram-negative pathogens. AT outer membrane (OM) secretion appears simple in many regards, yet the mechanism that enables transport of the central AT 'passenger' across the OM remains unclear. OM secretion efficiency for two AT passengers is enhanced by approximately 20 kDa stable core at the C-terminus of the passenger, but studies on a broader range of AT proteins are needed in order to determine whether a stability difference between the passenger N- and C-terminus represents a truly common mechanistic feature. Yersinia pestis YapV is homologous to Shigella flexneri IcsA, and like IcsA, YapV recruits mammalian neural Wiskott-Aldrich syndrome protein (N-WASP). In vitro, the purified YapV passenger is functional and rich in β-sheet structure, but lacks a approximately 20 kDa C-terminal stable core. However, the N-terminal 49 residues of the YapV passenger globally destabilize the entire YapV passenger, enhancing its OM secretion efficiency. These results indicate that the contributions of AT passenger sequences to OM secretion efficiency extend beyond a C-terminal stable core, and highlight a role of the passenger N-terminus in reducing passenger stability in order to facilitate OM secretion of some AT proteins.
authors.affiliation: Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Besingi
authors.forename: Julie L
authors.initials: JL
authors.lastname: Chaney
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Clark
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058947:Bacterial Secretion Systems; D002942:Circular Dichroism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism*; D015010:Yersinia pestis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D026901:Membrane Transport Proteins; D051316:Wiskott-Aldrich Syndrome Protein