Molecular mechanism for the recognition of sequence-divergent CIF peptides by the plant receptor kinases GSO1/SGN3 and GSO2

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The plant leucine-rich repeat receptor kinases GSO1/SGN3 and its peptide ligands CIF1 and CIF2 are essential for the formation of the Casparian strip. The Hothorn group from the Department of Botany and Plant Biology, in collaboration with the Geldner group from UNIL, has now uncovered in molecular detail how the SCHENGEN 3 receptor complex tightly binds CIF1 and CIF2.

Crystal structure of the GSO1/SGN3–CIF complex reveals a binding pocket for sulfotyrosine and extended back-bone interactions with CIF2. Structure-guided sequence analysis allowed to uncover previously uncharacterized CIF peptides conserved among higher plants. Quantitative binding assays with known and novel CIFs suggest that the homologous LRR-RKs GSO1/SGN3 and GSO2 have evolved unique peptide binding properties to control different developmental processes. A quantitative biochemical interaction screen, a CIF peptide antagonist and genetic analyses together implicate SERK proteins as essential coreceptor kinases required for GSO1/SGN3 and GSO2 receptor activation.

This work provides a mechanistic framework for the recognition of sequence-divergent peptide hormones in plants and was published in PNAS on January 21, 2020.

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Toxoplasmosis rids its host of all fear

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Toxoplasma gondii is a neurotropic parasite that infects all warm-blooded animals, including humans. Its objective is to reach the intestines of felids, the definitive host in which it reproduces sexually. To do so, the parasite first infects mice and drastically alters their behaviour. The natural aversion of mice toward cats is decreased – a phenomenon called fatal attraction – making them easy preys.

Using a set of complementary behavioral tests, Ivan Rodriguez and Dominique Soldati-Favre groups showed that T. gondii lowers general anxiety in infected mice, increases explorative behaviors, and surprisingly alters predator aversion without selectivity toward felids.

Their findings refute the myth of a selective loss of cat fear in T. gondii-infected mice and point toward widespread immune-related alterations of behaviors.

The study was published in Cell Reports on January 14, 2020.

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A novel protease contributes to the repair of DNA-protein crosslinks

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DNA-protein crosslinks (DPCs) are formed in the course of normal cell metabolism. However, their prolonged persistence can be extremely toxic, cause genome instability and promote diseases such as cancer.

The Stutz laboratory, together with the Kornmann (University of Oxford) and Loewith groups,describes a new mechanism required for the efficient DPC disassembly. Through a yeast genetic screen, Serbyn and collaborators identified the enigmatic Ddi1 protease as a new candidate degrading the protein moiety of DPCs. The authors show that Ddi1 helps to resolve a broad variety of DNA-protein crosslinks and functions independently of the known pathways involved in proteolytic DPC elimination.

Loss of Ddi1 sensitizes cells to several compounds that trap DPCs, including approved anti-cancer drugs. The latter provides novel insights into the putative mechanisms of drug resistance often observed in therapeutics.

The study was published in Molecular Cell on January 2, 2020.

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