Figure 2.

PE/PPE and ESX proteins. (A) Classification of PE/PPE proteins. PE/PPE proteins are broadly divided into PE and PPE proteins based on their characteristic N-terminal proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) sequences. These motifs occur within a span of ∼110 aminoacids in PE proteins and ∼180 aminoacids in PPE proteins. The PE family is further subdivided into two groups based on the presence or absence of a C-terminal domain with multiple tandem repeats of Gly-Gly-Ala or Gly-Gly -Asn sequences (PGRS, polymorphic GC-rich repetitive sequences). The PPE family is subdivided into three groups based on characteristic motifs in their C-termini, as indicated. (B) General features of ESX secretion systems. Organization of genes in the ESX-3 cluster, which induced maximal responses in the CD4+ T cell screen, are shown along with a schematic of a typical ESX or type VII secretion system. All ESX clusters contain a pair of Esx genes, the products of which form 1:1 complexes that are secreted. ESX clusters can exist as either complete (designated ESX-1 through ESX-5 systems) or partial clusters. In addition to the two Esx genes, complete ESX clusters encode four core components (ESX core component, Ecc) which are EccA (an ATPase), EccB (a membrane protein), EccC (an ATPase), EccD (a transmembrane protein), EccE (a transmembrane protein), and EccF (MycP, a subtilisin-like serine protease). Based on the current model of type VII secretion system, Esx heterodimers are recognized by EccC which then form an active ATPase providing energy for transport. EccC then propels these substrates through EccD, the transmembrane protein forming the export channel. MycP might be involved in processing certain substrates. The channel that transports the substrates thought the mycolate layer is yet to be identified. ESX clusters contain additional genes that code for other proteins called ESX secretion-associated proteins (Esp). In most of the complete and incomplete ESX systems, a pair of genes that code for PE/PPE proteins also exists in close proximity to the Esx genes.