Pathogenic Neisseria species, the causative agents of gonorrhoea and
bacterial meningitis, encode a family of polymorphic exo-
proteins which are autoproteolytically processed into several distinct extracellular components, including an
IgA1 protease and an alpha-
protein.
IgA1 protease, a putative virulence determinant, is a sequence-specific
endopeptidase known to cleave human
IgA1, but additional target
proteins have been postulated. The physical linkage of
IgA1 protease and alpha-
protein suggests a functional relationship of both precursor components. Previous work has shown that alpha-
protein is essential neither for extracellular transport nor for the proteolytic activity of
IgA1 protease. Intriguingly, alpha-
proteins carry amino acid sequences reminiscent of nuclear location signals of viral and eukaryotic
proteins. Here we demonstrate the functionality of these nuclear location
signal sequences in transfected eukaryotic cells. Chimeric alpha-
proteins show nuclear transport and selectively associate with nucleolar structures. More importantly, native purified alpha-
proteins are capable of entering certain human primary cells from the exterior via an endocytotic route and accumulate in the nuclei. The neisserial alpha-
proteins share several features with eukaryotic
transcription factors, such as the formation of dimers via a heptad repeat sequence. We propose a role for alpha-
proteins in the regulation of host-cell functions. As the alpha-
proteins are covalently connected with
IgA1 protease they may also serve as carries for the
IgA1 protease into human cells where additional proteolytic targets may exist. Neisseria meningitidis, which locally colonizes the nasopharyngeal mucosa of many human individuals without apparently causing symptoms, secretes this nucleus-targeted factor in large quantities.