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Conservation in Aspergillus fumigatus of pH‐signaling seven transmembrane domain and arrestin proteins, and implications for drug discovery
Author(s) -
Bignell Elaine M.
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06814.x
Subject(s) - biology , signal transduction , aspergillus fumigatus , extracellular , transmembrane protein , microbiology and biotechnology , signal peptide , fungal protein , biochemistry , yeast , receptor , gene , saccharomyces cerevisiae , peptide sequence
Adaptation to extracellular pH is a major challenge to fungal pathogens that infect mammalian hosts. Among pH responses mounted by diverse fungal pathogens there is a high degree of molecular conservation. This, coupled with the absence of such signaling pathways in mammalian cells, suggests that this crucial fungal survival mechanism might provide a useful means of limiting a broad spectrum of infectious fungal growth. PacC/Rim signaling converts extracellular cues, perceived by the fungal cell at extremes of ambient pH, into a cellular signal moderating the activation and/or derepression of multiple pH‐sensitive gene functions including enzymes, permeases, and transporters. Signal transduction via the fungal PacC/Rim pathway involves a seven transmembrane domain (7TMD) receptor–arrestin protein complex. This review will discuss, with particular attention to Aspergillus fumigatus (the major mold pathogen of humans), the conservation of PacC/Rim signal reception proteins, and protein domains, required for tolerance of pH change, and pathogenicity, and the significance of such molecules as targets for interventive therapies.