A fungus-specific protein domain is essential for Ras-Amediated morphogenetic signaling in Aspergillus fumigatus

Qusai Al Abdallah, Tiffany S. Norton, Amy M. Hill, Lawrence L. LeClaire, Jarrod Fortwendel

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Ras proteins function as conserved regulators of eukaryotic growth and differentiation and are essential signaling proteins orchestrating virulence in pathogenic fungi. Here, we report the identification of a novel N-terminal domain of the RasA protein in the filamentous fungus Aspergillus fumigatus. Whereas this domain is absent in Ras homologs of higher eukaryotes, the N-terminal extension is conserved among fungi and is characterized by a short string of two to eight amino acids terminating in an invariant arginine. For this reason, we have termed the RasA N-terminal domain the invariant arginine domain (IRD). Through mutational analyses, the IRD was found to be essential for polarized morphogenesis and asexual development, with the invariant arginine residue being most essential. Although IRD truncation resulted in a nonfunctional Ras phenotype, IRD mutation was not associated with mislocalization of the RasA protein or significant changes in steady-state RasA activity levels. Mutation of the RasA IRD diminished protein kinase A (PKA) activation and resulted in decreased interaction with the Rho-type GTPase, Cdc42. Taken together, our findings reveal novel, fungus-specific mechanisms for Ras protein function and signal transduction.

Original languageEnglish (US)
Article numbere00234-16
JournalmSphere
Volume1
Issue number6
DOIs
StatePublished - Nov 1 2016

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Aspergillus fumigatus
Arginine
Fungi
ras Proteins
rho GTP-Binding Proteins
Mutation
Cyclic AMP-Dependent Protein Kinases
Protein Domains
Eukaryota
Morphogenesis
Virulence
Signal Transduction
Proteins
Phenotype
Amino Acids
Growth

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

A fungus-specific protein domain is essential for Ras-Amediated morphogenetic signaling in Aspergillus fumigatus. / Abdallah, Qusai Al; Norton, Tiffany S.; Hill, Amy M.; LeClaire, Lawrence L.; Fortwendel, Jarrod.

In: mSphere, Vol. 1, No. 6, e00234-16, 01.11.2016.

Research output: Contribution to journalArticle

Abdallah, Qusai Al ; Norton, Tiffany S. ; Hill, Amy M. ; LeClaire, Lawrence L. ; Fortwendel, Jarrod. / A fungus-specific protein domain is essential for Ras-Amediated morphogenetic signaling in Aspergillus fumigatus. In: mSphere. 2016 ; Vol. 1, No. 6.
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