{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Trinidad DD"],"funding":["NIAID NIH HHS","NIGMS NIH HHS"],"pubmed_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 <i>M. tuberculosis</i> survival, is a promising target. In this study, we perform a deep mutational scan on the ESX-3 core protein EccD<sub>3</sub> in the model organism <i>M. smegmatis</i>. 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 EccD<sub>3</sub>. Our data combined with structural comparisons to ESX-5 complexes support a model where EccD<sub>3</sub> stabilizes the complex, with the hinge motif within the linker being particularly sensitive to disr"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.08.23.609456"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11370616"],"repository":["biostudies-literature"],"pubmed_title":["Deep mutational scanning of EccD<sub>3</sub> reveals the molecular basis of its essentiality in the mycobacterium ESX secretion system."],"pmcid":["PMC11370616"],"funding_grant_id":["F32 GM152977","R35 GM145238","F31 AI157438"],"pubmed_authors":["Coyote-Maestas W","Macdonald CB","Trinidad DD","Fraser JS","Rosenberg OS"],"additional_accession":[]},"is_claimable":false,"name":"Deep mutational scanning of EccD<sub>3</sub> reveals the molecular basis of its essentiality in the mycobacterium ESX secretion system.","description":"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 <i>M. tuberculosis</i> survival, is a promising target. In this study, we perform a deep mutational scan on the ESX-3 core protein EccD<sub>3</sub> in the model organism <i>M. smegmatis</i>. 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 EccD<sub>3</sub>. Our data combined with structural comparisons to ESX-5 complexes support a model where EccD<sub>3</sub> stabilizes the complex, with the hinge motif within the linker being particularly sensitive to disr","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-04-21T03:28:09.964Z","creation":"2025-04-06T14:24:14.191Z"},"accession":"S-EPMC11370616","cross_references":{"pubmed":["39229178"],"doi":["10.1101/2024.08.23.609456"]}}