Imperial College London
Emeritus Professor Herb Arst

Emeritus ProfessorHerbArst

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor of Microbial Genetics
 
 
 
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Contact

 

+44 (0)20 7594 2073h.arst

 
 
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Location

 

5.40Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Arst:2016:10.111/mmi13438,
author = {Arst, HN and Lucena-Agell, D and Hervas-Aguilar, A and Munera-Huertas, T and Pougovkina, O and Rudnicka, J and Galindo, A and Tilburn, J and Penalva, MA},
doi = {10.111/mmi13438},
journal = {Molecular Microbiology},
pages = {982--1002},
title = {Mutational analysis of the Aspergillus ambient pH receptor PalH underscores its potential as a target for antifungal compounds},
url = {http://dx.doi.org/10.111/mmi13438},
volume = {101},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The pal/RIM ambient pH signalling pathway is crucial for the ability of pathogenic fungi to infect hosts. The Aspergillus nidulans 7TMD 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 ambientexposed region comprising the extracellular loop connecting TM4TM5 and ambientproximal 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 Pro316dependent transition between inactive and active PalH conformations, governed by an ambientexposed 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.v
AU  - Arst,HN
AU  - Lucena-Agell,D
AU  - Hervas-Aguilar,A
AU  - Munera-Huertas,T
AU  - Pougovkina,O
AU  - Rudnicka,J
AU  - Galindo,A
AU  - Tilburn,J
AU  - Penalva,MA
DO  - 10.111/mmi13438
EP  - 1002
PY  - 2016///
SN  - 0950-382X
SP  - 982
TI  - Mutational analysis of the Aspergillus ambient pH receptor PalH underscores its potential as a target for antifungal compounds
T2  - Molecular Microbiology
UR  - http://dx.doi.org/10.111/mmi13438
UR  - http://hdl.handle.net/10044/1/33652
VL  - 101
ER  -
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