title: Of linkers and autochaperones: an unambiguous nomenclature to identify common and uncommon themes for autotransporter secretion.
abstract: Autotransporter (AT) proteins provide a diverse array of important virulence functions to Gram-negative bacterial pathogens, and have also been adapted for protein surface display applications. The 'autotransporter' moniker refers to early models that depicted these proteins facilitating their own translocation across the bacterial outer membrane. Although translocation is less autonomous than originally proposed, AT protein segments upstream of the C-terminal transmembrane β-barrel have nevertheless consistently been found to contribute to efficient translocation and/or folding of the N-terminal virulence region (the 'passenger'). However, defining the precise secretion functions of these AT regions has been complicated by the use of multiple overlapping and ambiguous terms to define AT sequence, structural, and functional features, including 'autochaperone', 'linker' and 'junction'. Moreover, the precise definitions and boundaries of these features vary among ATs and even among research groups, leading to an overall murky picture of the contributions of specific features to translocation. Here we propose a unified, unambiguous nomenclature for AT structural, functional and conserved sequence features, based on explicit criteria. Applied to 16 well-studied AT proteins, this nomenclature reveals new commonalities for translocation but also highlights that the autochaperone function is less closely associated with a conserved sequence element than previously believed.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Drobnak
authors.forename: Esther
authors.initials: E
authors.lastname: Braselmann
authors.forename: Julie L
authors.initials: JL
authors.lastname: Chaney
authors.forename: Denisse L
authors.initials: DL
authors.lastname: Leyton
authors.forename: Harris D
authors.initials: HD
authors.lastname: Bernstein
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
authors.forename: Joen
authors.initials: J
authors.lastname: Luirink
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Clark
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D018832:Molecular Chaperones; D037521:Virulence Factors