Species-specific secretion of ESX-5 type VII substrates is determined by the linker 2 of EccC 5 .

Autor: Bunduc CM; Section Molecular Microbiology, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Ummels R; Department of Medical Microbiology and Infection Control, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Amsterdam, The Netherlands., Bitter W; Section Molecular Microbiology, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Department of Medical Microbiology and Infection Control, Amsterdam Infection & Immunity Institute, Amsterdam UMC, Amsterdam, The Netherlands., Houben ENG; Section Molecular Microbiology, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Molecular microbiology [Mol Microbiol] 2020 Jul; Vol. 114 (1), pp. 66-76. Date of Electronic Publication: 2020 Mar 09.
DOI: 10.1111/mmi.14496
Abstrakt: Mycobacteria use type VII secretion systems (T7SSs) to translocate a wide range of proteins across their diderm cell envelope. These systems, also called ESX systems, are crucial for the viability and/or virulence of mycobacterial pathogens, including Mycobacterium tuberculosis and the fish pathogen Mycobacterium marinum. We have previously shown that the M. tuberculosis ESX-5 system is unable to fully complement secretion in an M. marinum esx-5 mutant, suggesting species specificity in secretion. In this study, we elaborated on this observation and established that the membrane ATPase EccC 5 , possessing four (putative) nucleotide-binding domains (NBDs), is responsible for this. By creating M. marinum-M. tuberculosis EccC 5 chimeras, we observed both in M. marinum and in M. tuberculosis that secretion specificity of PE_PGRS proteins depends on the presence of the cognate linker 2 domain of EccC 5 . This region connects NBD1 and NBD2 of EccC 5 and is responsible for keeping NBD1 in an inhibited state. Notably, the ESX-5 substrate EsxN, predicted to bind to NBD3 on EccC 5 , showed a distinct secretion profile. These results indicate that linker 2 is involved in species-specific substrate recognition and might therefore be an additional substrate recognition site of EccC 5 .
(© 2020 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: