Deep mutational scanning of EccD₃ reveals the molecular basis of its essentiality in the mycobacterium ESX secretion system.

ABSTRACT: Tuberculosis remains the deadliest infectious disease in the world and requires novel therapeutic targets. The ESX-3 secretion system, which is essential for iron and zinc homeostasis and thus M. tuberculosis survival, is a promising target. In this study, we perform a deep mutational scan on the ESX-3 core protein EccD₃ in the model organism M. smegmatis. We systematically investigated the functional roles of 145 residues across the soluble ubiquitin-like domain, the conformationally distinct flexible linker, and selected transmembrane helices of EccD₃. Our data combined with structural comparisons to ESX-5 complexes support a model where EccD₃ stabilizes the complex, with the hinge motif within the linker being particularly sensitive to disr

SUBMITTER: Trinidad DD 

PROVIDER: S-EPMC11370616 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature