Events

EPS Flying Seminar :AI guided discovery of autophagy modulating pathogen effectors

Date: 14 June

Time: 11:00 – 12:00*,

Location: Wageningen University, exact location will be announced

Organizer: EPS and Mireille van Damme

*please send an email to mireille.vandamme@wur.nl if you are interested to talk to Tolga during lunch after the presentation

Abstract

 Autophagy is an intracellular degradation process central to cellular homeostasis and defense against plant pathogens. Regulation of autophagy relies on hierarchical binding of autophagy cargo receptors and adaptors to the core autophagy protein ATG8. Modulators of autophagy often contain a conserved short linear sequence called the ATG8 interacting motif (AIM), which is responsible for mediating interactions with ATG8. We recently developed a fast-forward pipeline that is based on protein modelling using Alphafold2-multimer (AF2-multimer) to identify and validate both canonical and atypical AIMs with a high level of accuracy. Here, by combining protein modelling data with phylogenetic analysis of protein sequences and protein–protein interaction assays, we demonstrate that AF2-multimer predicts pathogen effectors that modulate autophagy. We identified a plethora of autophagy modulating effectors from around hundred pathogen genomes. We experimentally validated and functionally characterized couple of these effectors using cell biology, genetics, and biophysical assays, revealing unprecedented insights into molecular basis of autophagy modulation by plant pathogens. AF2-multimer guided discovery of autophagy targeting effectors will significantly accelerate our understanding of how plant pathogens manipulate host autophagy machinery, paving the way for novel strategies for disease control.