title: Characterization of differential pore-forming activities of ESAT-6 proteins from Mycobacterium tuberculosis and Mycobacterium smegmatis.
abstract: Mycobacterium tuberculosis ESAT-6 (MtbESAT-6) plays essential roles in pathogenesis. MtbESAT-6 exhibits a unique pore-forming activity (PFA) that is not found in its ortholog from non-pathogenic Mycobacterium smegmatis (MsESAT-6). Here, we characterized the differential PFAs and found that exchange of I25-H26/T25-A26 between two proteins reciprocally affected their PFAs. MtbESAT-6(IH/TA) had ~ 40% reduction, while MsESAT-6(TA/IH) fully acquired its activity similar to MtbESAT-6. Mutations of A17E, K38T, N67L or R74Q on MtbESAT-6(IH/TA) further reduced the activity, with MtbESAT-6(IH/TA-17) being the lowest. This study suggests I25-H26 as the pH-sensor essential for MsESAT-6 to fully acquire the activity, while multiple residues contributed to MtbESAT-6 PFA.
authors.affiliation: Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction, Ministry of Education, Huazhong Agriculture University, Wuhan, China.|Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, TX, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, TX, USA.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, TX, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, TX, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Sino-Duth Biomedical and Information Engineering School of Northeastern University, Shenyang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, TX, USA.|Sino-Duth Biomedical and Information Engineering School of Northeastern University, Shenyang, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009154:Mutation; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018272:Porins
keywords: ESAT-6; Mycobacterium tuberculosis; pathogenesis; pore-forming activity; virulence factor