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Identification of Host Pathways Targeted by Bacterial Effector Proteins using Yeast Toxicity and Suppressor Screens
Published on: October 25, 2019
Fungal effector Ecp6 outcompetes host immune receptor for chitin binding through intrachain LysM dimerization
Andrea Sánchez-Vallet1, Raspudin Saleem-Batcha, Anja Kombrink
1Centro de Biotecnología y Genómica de Plantas , Universidad Politécnica de Madrid , Madrid , Spain ; Laboratory of Phytopathology , Wageningen University , Wageningen , Netherlands.
Abstract:
While host immune receptors detect pathogen-associated molecular patterns to activate immunity, pathogens attempt to deregulate host immunity through secreted effectors. Fungi employ LysM effectors to prevent recognition of cell wall-derived chitin by host immune receptors, although the mechanism to compete for chitin binding remained unclear. Structural analysis of the LysM effector Ecp6 of the fungal tomato pathogen Cladosporium fulvum reveals a novel mechanism for chitin binding, mediated by intrachain LysM dimerization, leading to a chitin-binding groove that is deeply buried in the effector protein. This composite binding site involves two of the three LysMs of Ecp6 and mediates chitin binding with ultra-high (pM) affinity. Intriguingly, the remaining singular LysM domain of Ecp6 binds chitin with low micromolar affinity but can nevertheless still perturb chitin-triggered immunity. Conceivably, the perturbation by this LysM domain is not established through chitin sequestration but possibly through interference with the host immune receptor complex. DOI:http://dx.doi.org/10.7554/eLife.00790.001.
Insights
Fungal LysM effectors, like Ecp6, bind chitin with ultra-high affinity using a unique dimerization mechanism. This prevents host immune detection, revealing a novel fungal immune evasion strategy.
Area of Science:
- Plant-pathogen interactions
- Molecular mechanisms of immunity
- Fungal biology
Background:
- Pathogens secrete effectors to evade host immunity.
- Fungal LysM effectors bind chitin, a component of fungal cell walls.
- The precise mechanism of LysM effector chitin binding and immune interference was unclear.
Purpose of the Study:
- To elucidate the structural mechanism of chitin binding by the fungal LysM effector Ecp6.
- To understand how Ecp6 competes with host immune receptors for chitin recognition.
- To investigate the role of individual LysM domains in Ecp6 function.
Main Methods:
- X-ray crystallography to determine the structure of Ecp6.
- Biochemical assays to measure chitin-binding affinity.
- Functional studies to assess Ecp6's impact on chitin-triggered immunity.
Main Results:
- Ecp6 utilizes intrachain LysM dimerization to form a composite, deeply buried chitin-binding groove with ultra-high (pM) affinity.
- Two LysM domains are involved in this high-affinity binding.
- A separate LysM domain binds chitin with lower affinity (µM) but still perturbs host immunity, likely via non-sequestration mechanisms.
Conclusions:
- Fungal LysM effectors have evolved sophisticated mechanisms for high-affinity chitin binding to evade host immunity.
- Ecp6's composite binding site represents a novel mode of effector-mediated immune suppression.
- The dual-affinity binding of Ecp6 suggests complex strategies for fungal pathogenesis and host immune interference.
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