Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease

Abstract

Several human bacterial pathogens, including the Gram-negative diplococcus Neisseria gonorrhoeae, produce extracellular proteases that are specific for human immunoglobulin IgA1. Immunoglobulin A (IgA) proteases have been studied extensively and the genes of some species cloned in Escherichia coli, but their role in pathogenesis remains unclear. Recently we derived a DNA fragment of 5 kilobases (kb) from N. gonorrhoeae MS11 directing extracellular active enzyme in E. coli. Although the mature enzyme of strain MS11 was shown to have a relative molecular mass of 106,000 (Mr 106K) in gels, the DNA sequence of this cloned fragment reveals a single gene coding for a 169K precursor of IgA protease. The precursor contains three functional domains, the amino-terminal leader which is assumed to initiate the inner membrane transport of the precursor, the protease, and a carboxyl-terminal 'helper' domain apparently required for extracellular secretion (excretion). Based on the structural features of the precursor, we propose a model in which the helper serves as a pore for excretion of the protease domain through the outer membrane. IgA protease acquires an active conformation as its extracellular transport proceeds and is released as a proform from the membrane-bound helper by autoproteolysis. The soluble proform further matures into the 106 K IgA protease and a small stable alpha-protein.

Autotransported Serine Protease A of Neisseria meningitidis : an Immunogenic, Surface-Exposed Outer Membrane, and Secreted Protein

“…Since the first description of IgA1 protease of N. gonorrhoeae by Pohlner et al (26), an increasing number of proteins have been discovered in various gram-negative organisms, which share the same mechanism of transportation, sometimes cess were then examined for the presence of the characteristic features of autotransporter proteins and for homology to known autotransporter proteins. We identified a novel putative autotransporter protein, which was designated AspA in view of its N-terminal homology to the autotransported serine proteases PrtT and PrtS, and their homologues, Ssp-H1 and Ssp-H2, in S. marcescens.…”

“…AutB is probably a pseudogene (2). The autotransporter mechanism of protein transportation and secretion was first described for the immunoglobulin A1 (IgA1) proteases of pathogenic Neisseria (26) and is a rapidly expanding family of proteins (14,15). The characteristic structure of autotransporter proteins and the secretion mechanism have been reviewed elsewhere (15,17).…”

A conserved stable core structure in the passenger domain β‐helix of autotransporter virulence proteins

“…1 Several labs have hypothesized that OM secretion of the passenger proceeds from C?N terminus. [10][11][12] In this scenario, extra stability at the C-terminus of the passenger might produce a folding template or nucleus that could promote the folding of the remainder of the b-helix during OM secretion.…”

Mechanistic link between β barrel assembly and the initiation of autotransporter secretion

“…Early experiments in which the β domain was deleted showed that it plays an essential role in translocation and led to the proposal that it forms a channel through which the covalently linked passenger domain is secreted (15). Recently, however, several findings have challenged the "autotransporter" hypothesis.…”