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International audience; Tuberculosis claims significantly more than one million lives each year. A feasible way to face the issue of drug resistance is the development of new antibiotics. Bacterial uridine 5’-monophosphate (UMP) kinase is a promis- ing target for novel antibiotic discovery as it is essential for bacterial sur- vival and has no counterpart in human cells. The UMP kinase from M. tuberculosis is also a model of particular interest for allosteric regula- tion with two effectors, GTP (positive) and UTP (negative). In this study, using X-ray crystallography and cryo-electron microscopy, we report for the first time a detailed description of the negative effector UTP-binding site of a typical Gram-positive behaving UMP kinase. Comparison between this snapshot of low affinity for Mg-ATP with our previous 3D-structure of the GTP-bound complex of high affinity for Mg-ATP led to a better understanding of the cooperative mechanism and the allosteric regulation of UMP kinase. Thermal shift assay and circular dichroism experiments corroborate our model of an inhibition by UTP linked to higher flexibility of the Mg-ATP-binding domain. These new structural insights provide valuable knowledge for future drug discovery strategies targeting bacterial UMP kinases.

National audience; Many plant viruses of agricultural importance are transmitted to host plants by noncirculative aphid transmission, meaning that viruses do not penetrate the aphid body but are retained on the cuticle of the insect and released and inoculated into a new host plant together with the aphid saliva. Recently, our collaborators have reported the identification of two closely related and highly conserved RR-1 cuticular proteins, Stylin-01 and Stylin-02, in the acrostyle of both Myzus persicae and Acyrthosiphon pisum. Stylin-01 and Stylin-02 belong to the CPR proteins, cuticular proteins bearing the Rebers and Riddiford consensus sequence (RR). They showed that Stylin-01 is involved in CaMV transmission and could be the prime candidate receptor for the vector transmission of noncirculative plant viruses. CPR proteins in aphids can be divided into subgroups RR-1, RR-2, and RR-3, proteins of RR-2 being also detected within the acrostyle. Deciphering virus–vector interactions at molecular level is essential to understand transmission mechanisms and develop new strategies to control viral spread. In this context, we decided to perform a structural characterization of various proteins belonging to the RR1 subgroup of CPRs, including Stylin-1 and 2. From predictive models, nuclear magnetic resonance experiments and molecular dynamics, we propose a structural model for this family of proteins.