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The citron homology domain as a scaffold for Rho1 signaling

DOI: 10.1073/pnas.2110298118 DOI Help

Authors: Sergio G. Bartual (University of Dundee) , Wenfan Wei (University of Dundee) , Yao Zhou (Guangxi University; Guangxi Academy of Sciences) , Veronica M. Pravata (University of Dundee) , Wenxia Fang (University of Dundee; Guangxi Academy of Sciences) , Kaizhou Yan (University of Dundee) , Andrew T. Ferenbach (University of Dundee) , Deborah E. A. Lockhart (University of Aberdeen) , Daniel Van Aalten (University of Dundee)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 118

State: Published (Approved)
Published: September 2021
Diamond Proposal Number(s): 10071

Open Access Open Access

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.

Journal Keywords: Aspergillus fumigatus; structural biology; signal transduction; cell wall; citron homology domain

Diamond Keywords: Fungi

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

Added On: 27/09/2021 09:53


Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Infectious Diseases Pathogens Structural biology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)