The citron homology domain as a scaffold for Rho1 signaling

Sergio G. Bartual, Wenfan Wei, Yao Zhou, Veronica M. Pravata, Wenxia Fang, Kaizhou Yan, Andrew T. Ferenbach, Deborah E. A. Lockhart, Daan M. F. van Aalten (Lead / Corresponding author)

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Abstract

Aspergillus fumigatus is a human opportunistic pathogen showing emerging resistance against a limited repertoire of antifungal agents available. The GTPase Rho1 has been identified as an important regulator of the cell wall integrity signaling pathway that regulates the composition of the cell wall, a structure that is unique to fungi and serves as a target for antifungal compounds. Rom2, the guanine nucleotide exchange factor to Rho1, contains a C-terminal citron homology (CNH) domain of unknown function that is found in many other eukaryotic genes. Here, we show that the Rom2 CNH domain interacts directly with Rho1 to modulate β-glucan and chitin synthesis. We report the structure of the Rom2 CNH domain, revealing that it adopts a seven-bladed β-propeller fold containing three unusual loops. A model of the Rho1-Rom2 CNH complex suggests that the Rom2 CNH domain interacts with the Rho1 Switch II motif. This work uncovers the role of the Rom2 CNH domain as a scaffold for Rho1 signaling in fungal cell wall biosynthesis.

Original languageEnglish
Article numbere2110298118
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number39
Early online date20 Sep 2021
DOIs
Publication statusPublished - 28 Sep 2021

Keywords

  • Aspergillus fumigatus
  • cell wall
  • Rom2
  • CNH domain
  • AfRho1
  • protein-protein interaction
  • Signal transduction
  • Citron homology domain
  • Cell wall
  • Structural biology

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