On how a transcription factor can avoid its proteolytic activation in the absence of signal transduction

In response to alkaline ambient pH, the Aspergillus nidulans PacC transcription factor mediating pH regulation of gene expression is activated by proteolytic removal of a negative-acting C–terminal domain. We demonstrate interactions involving the ∼150 C–terminal PacC residues and two regions located immediately downstream of the DNA binding domain. Our data indicate two full-length PacC conformations whose relative amounts depend upon ambient pH: one ‘open’ and accessible for processing, the other ‘closed’ and inaccessible. The location of essential determinants for proteolytic processing within the two more upstream interacting regions probably explains why the interactions prevent processing, whereas the direct involvement of the C–terminal region in processing-preventing interactions explains why C–terminal truncating mutations result in alkalinity mimicry and pH-independent processing. A mutant PacC deficient in pH signal response and consequent processing behaves as though locked in the ‘closed’ form. Single-residue substitutions, obtained as mutations bypassing the need for pH signal transduction, identify crucial residues in each of the three interactive regions and overcome the processing deficiency in the ‘permanently closed’ mutant

Glycosylphosphatidylinositols synthesized by Trichophyton rubrum in a cell-free system. Nachweis von Glykosylphosphatidylinositolen von Trichophyton rubrum synthetisiert im zellfreien System

Pusch U, Effendy I, Schwarz RT, Azzouz N. Glycosylphosphatidylinositols synthesized by Trichophyton rubrum in a cell-free system. Mycoses. 2003;46(3-4):104-113.The opportunistic fungi Trichophyton rubrum and T. mentagrophytes , are responsible for relatively non-inflammatory chronic dermatophytes infections in immunocompromised patients but also in healthy individuals. This chronic infection is associated with immunosuppressive effects of the cell wall components particularly the polysaccharides secreted by these organisms. We have studied glycosylphosphatidylinositol (GPI) anchor biosynthesis in the pathogenic fungus T. rubrum and could demonstrate that T. rubrum is able to synthesize GPI structures. Glycolipids synthesized in a cell-free system prepared from the dermatophyte T. rubrum and labeled with [(3) H]mannose, and [(3) H]galactose using GDP-[(3) H]mannose and UDP-[(3) H]galactose, respectively, were identified and structurally characterized as GPIs. The evolutionary conserved backbone of T. rubrum GPIs incorporates galactose. Further, all glycolipids lack the acyl group on the inositol which was shown for Saccharomyces cerevisiae and mammalian GPIs. Our data suggest significant differences in the GPI biosynthetic pathway between mammalian and T. rubrum cells that could perhaps be exploited for the development of an antimycotic for Trichophyton infection

Impact of the Environment upon the Candida albicans Cell Wall and Resultant Effects upon Immune Surveillance

Acknowledgements This work was funded by a programme grant from the UK Medical Research Council [www.mrc.ac.uk: MR/M026663/1], and by PhD studentships from the University of Aberdeen to AP, DL. The work was also supported by the Medical Research Council Centre for Medical Mycology (MR/N006364/1) and by the Wellcome Trust [www.wellcome.ac.uk: 097377]. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.Postprin