English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/165709
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Mutational analysis of the Aspergillus ambient pH receptor PalH underscores its potential as a target for antifungal compounds

AuthorsLucena-Agell, Daniel CSIC ORCID ; Hervás-Aguilar, América CSIC; Múnera-Huertas, Tatiana; Pougovkina, Olga; Rudnicka, Joanna D.; Galindo, Antonio CSIC ORCID; Tilburn, Joan; Arst, Herbert Nathan Jr. CSIC ; Peñalva, Miguel Ángel CSIC ORCID
Issue Date15-Jul-2016
PublisherJohn Wiley & Sons
CitationMol Microbiol 101(6): 982–1002 (2016)
AbstractThe pal/RIM ambient pH signalling pathway is crucial for the ability of pathogenic fungi to infect hosts. The Aspergillus nidulans 7‐TMD receptor PalH senses alkaline pH, subsequently facilitating ubiquitination of the arrestin PalF. Ubiquitinated PalF triggers downstream signalling events. The mechanism(s) by which PalH transduces the alkaline pH signal to PalF is poorly understood. We show that PalH is phosphorylated in a signal dependent manner, resembling mammalian GPCRs, although PalH phosphorylation, in contrast to mammalian GPCRs, is arrestin dependent. A genetic screen revealed that an ambient‐exposed region comprising the extracellular loop connecting TM4‐TM5 and ambient‐proximal residues within TM5 is required for signalling. In contrast, substitution by alanines of four aromatic residues within TM6 and TM7 results in a weak ‘constitutive’ activation of the pathway. Our data support the hypothesis that PalH mechanistically resembles mammalian GPCRs that signal via arrestins, such that the relative positions of individual helices within the heptahelical bundle determines the Pro316‐dependent transition between inactive and active PalH conformations, governed by an ambient‐exposed region including critical Tyr259 that potentially represents an agonist binding site. These findings open the possibility of screening for agonist compounds stabilizing the inactive conformation of PalH, which might act as antifungal drugs against ascomycetes.
Description21 p.-11 fig.-1 tab.
Publisher version (URL)http://dx.doi.org/10.1111/mmi.13438
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
Lucena-Agell_et_al-2016-Molecular_Microbiology.pdfArtículo principal1,6 MBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.