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Aspergillus Protein Degradation Pathways with Different Secreted Protease Sets at Neutral and Acidic pH

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Department of Dermatology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland, Protein Analysis Facility, Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland, Department of Medical Microbiology and National Reference Center for Systemic Mycoses, University Hospital of Göttingen, Germany, Division de Pharmacologie et Toxicologie Cliniques, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and Laboratory of Molecular and Cellular Biology, University of Neuchâtel, rue E-Argand 11, 2009 Neuchâtel, Switzerland
* To whom correspondence should be addressed. E-mail: [email protected]
†Department of Dermatology, Centre Hospitalier Universitaire Vaudois.
‡University of Lausanne.
§University Hospital of Göttingen.
∥Division de Pharmacologie et Toxicologie Cliniques, Centre Hospitalier Universitaire Vaudois.
⊥University of Neuchâtel.
Cite this: J. Proteome Res. 2010, 9, 7, 3511–3519
Publication Date (Web):May 20, 2010
Copyright © 2010 American Chemical Society

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    Aspergillus fumigatus grows well at neutral and acidic pH in a medium containing protein as the sole nitrogen source by secreting two different sets of proteases. Neutral pH favors the secretion of neutral and alkaline endoproteases, leucine aminopeptidases (Laps) which are nonspecific monoaminopeptidases, and an X-prolyl dipeptidase (DppIV). Acidic pH environment promotes the secretion of an aspartic endoprotease of pepsin family (Pep1) and tripeptidyl-peptidases of the sedolisin family (SedB and SedD). A novel prolyl peptidase, AfuS28, was found to be secreted in both alkaline and acidic conditions. In previous studies, Laps were shown to degrade peptides from their N-terminus until an X-Pro sequence acts as a stop signal. X-Pro sequences can be then removed by DppIV, which allows Laps access to the following residues. We have shown that at acidic pH Seds degrade large peptides from their N-terminus into tripeptides until Pro in P1 or P′1 position acts as a stop for these exopeptidases. However, X-X-Pro and X-X-X-Pro sequences can be removed by AfuS28 thus allowing Seds further sequential proteolysis. In conclusion, both alkaline and acidic sets of proteases contain exoprotease activity capable of cleaving after proline residues that cannot be removed during sequential digestion by nonspecific exopeptidases.

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