Structural and functional analysis of GPCRs and G-protein signaling during host-pathogen interaction of Ustilago maydis

• Applicant: Dr. Florian Altegoer
• Subject Area: Organismic Interactions, Chemical Ecology and Microbiomes of Plant Systems
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 551864487

Microorganisms have developed sophisticated strategies to sense and communicate with their environment. Plant-associated fungi often live in close contact and establish a tight interaction zone with their respective hosts resulting in an extensive crosstalk. This involves a continuous exchange of e.g. nutrients, metabolites and proteins but details on how fungi perceive and react to these signals are critically lacking. In this project, we now combined a sequence and structural bioinformatic analysis to generate a catalogue of fungal membrane proteins of the plant-pathogen Ustilago maydis produced during colonization of its host Zea mays. Our investigation revealed the presence of more than 30 previously undescribed proteins that share structural similarity with 7-transmembrane G-protein coupled receptors (GPCRs). This number extends way beyond the previously reported 7 GPCRs in U. maydis. Furthermore, U. maydis possesses four G-subunits, of which one termed Gpa3 has been demonstrated crucial for fungal development and plant colonization. However, the GPCRs coupled to Gpa3 could not be identified yet and details of how extracellular cues are precisely integrated via cAMP signaling are lacking. Structural complex modeling suggested that from our identified candidates, three GPCRs termed Glp6, Glp11 and Glp12 likely transmit their signals via Gpa3. Deletion strains of the individual receptor-encoding genes exhibit phenotypes comparable to the gpa3 deletion and at least one strain has reduced cAMP levels. Our computational structural approach therefore sets the stage for an in-depths analysis to investigate the signaling dynamics of these three Gpa3-coupled GPCRs. Furthermore, we will investigate how different extracellular signals are integrated into cellular responses via dynamic modulation of intracellular cAMP levels and identify the precise sets of ligands activating the different receptors. Collectively, our research will therefore provide the first mechanistic structure-function insights into GPCR-mediated host adaptation by plant pathogenic fungi and potentially reveal alternative approaches for disease control.

• DFG Programme: Research Grants