3.A.24.4.1
The Type VII secretion system (T7SS or MPSS); the ESAT-6-like protein secretion system, ESX-5 (Abdallah et al., 2006; Sayes et al., 2012; Houben et al. 2012).  Mediates the secretion of the EsxN, PPE [pro-pro-glu motif] and PE_PGRS proteins (Deng and Xie 2012).  The EccB5, EccC5, EccD5 and EccE5 proteins form a membrane complex of about 1.5 MDa while EccA5 may be the channel-forming subunit that exports the substrate proteins (Bunduc et al. 2021). Thus, ESX-5 exports protein substrate (Houben et al. 2012).  PE25/PPE41form a heterodimer that is targeted to the T7SS, ESX5, by a C-terminal signal in PE25 which is necessary but not sufficient for targeting to ESX5 (Daleke et al. 2012).  An esx-5 mutant is strongly impaired in the uptake and utilization of hydrophobic carbon sources. Possibly the ESX-5 system is responsible for the transport of cell envelope proteins that are required for nutrient uptake (Ates et al. 2015).  Mycobacterium tuberculosis releases membrane vesicles (MV) that modulate host immune responses and aid in iron acquisition, and the ESX-5 system seems to play a role, together with the SenX3-RegX3 complex which regulates the process (White et al. 2018). The 3-D structure of ESX-5 has been determined (Bunduc et al. 2021) (see ESX5 family description, paragraph 11 for details). The structure of the mycobacterial ESX-5 type VII secretion system pore complex has been determined (Beckham et al. 2021). The high-resolution structure of the 2.1-megadalton ESX-5 core complex captured a dynamic, secretion-competent conformation of the pore within a well-defined transmembrane section, sandwiched between two flexible protein layers at the cytosolic entrance and the periplasmic exit. Beckham et al. 2021 proposed that this flexibility endows the ESX-5 machinery with large conformational plasticity required to accommodate targeted protein secretion. A highly dynamic state of the pore may represent a fundamental principle of bacterial secretion machineries.