Figure 8.

Proposed model describing the importance of IDRs in PE–PPE proteins. The PE35–PPE68 protein pair gains structural order on forming complex. By virtue of gain in structural order, complex shows enhanced immunomodulatory effect to enhance pro‐pathogen immune response. Even though PPE68 (green) protein individually downregulated Th1 response, the structurally ordered complex of PE35–PPE68 (Blue) has an enhanced effect on downregulation of Th1 protective cytokines. Th1 cytokines (brown) are decreased, while Th2 cytokines (yellow) are enhanced, which in turn could likely increase the survival chances of M.tb. This suggests that M.tb is able to counterbalance reductive evolution by employing this specific family of proteins, exploiting the disorder‐to‐order transition. Being exposed on the pathogen surface and showing high levels of functional specialization among family members through variable segments, PE–PPE protein complexes successfully influence the host immune system toward favoring pathogen survival.