1887

Abstract

As with all classical monomeric autotransporters, IgA protease of is a modular protein consisting of an N-terminal signal sequence, a passenger domain and a C-terminal translocator domain (TD) that assists in the secretion of the passenger domain across the outer membrane. The passenger of IgA protease consists of three separate domains: the protease domain, the γ-peptide and the α-peptide that contains nuclear localization signals (NLSs). The protease domain is released into the extracellular milieu either via autocatalytic processing or via cleavage by another autotransporter, NalP, expression of which is phase-variable. NalP-mediated cleavage results in the release of a passenger that includes the α- and γ-peptides. Here, we studied the fate of the α-peptide when NalP was not expressed and observed strain-dependent differences. In meningococcal strains where the α-peptide contained a single NLS, the α-peptide remained covalently attached to the TD and was detected at the cell surface. In other strains, the α-peptide contained four NLSs and was separated from the TD by an IgA protease autoproteolytic cleavage site. In many of those cases, the α-peptide was found non-covalently associated with the cells as a separate polypeptide. The cell surface association of the α-peptides may be relevant physiologically. We report a novel function for the α-peptide, i.e. the binding of heparin – an immune-modulatory molecule that in the host is found in the extracellular matrix and connected to cell surfaces.

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2014-11-01
2019-11-16
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