title: Conservation in Aspergillus fumigatus of pH-signaling seven transmembrane domain and arrestin proteins, and implications for drug discovery.
abstract: 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.
authors.affiliation: Section of Microbiology, Faculty of Medicine, Imperial College London, London, UK. e.bignell@imperial.ac.uk
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Bignell
mesh_terms: D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D019390:Arrestins / Q000737:chemistry / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000378:metabolism*; D055808:Drug Discovery; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D000935:Antifungal Agents; D019390:Arrestins; D008565:Membrane Proteins