Structural basis of the PE–PPE protein interaction in Mycobacterium tuberculosis

• DOI: 10.1074/jbc.m117.802645
• Publication Date: 2017-08-24T00:30:24Z
• Authors: Xin Chen; Hiu-fu Cheng; Junwei Zhou; Chiu-yeung Chan; Kwok-fai Lau; Stephen Kwok-wing...; Shannon Wing-ngor Au
• Keywords: Chaperone (clinical); Human pathogen

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has developed multiple strategies to adapt human host. The five type VII secretion systems, ESX-1–5, direct export many virulence-promoting protein effectors across complex mycobacterial cell wall. One class ESX substrates is PE–PPE family proteins, which unique mycobacteria and essential for infection, antigenic variation, host–pathogen interactions. genome Mtb encodes 168 proteins. Many them are thought be secreted through ESX-5 system function in pairs. However, understanding specific pairing proteins their structure–function relationship limited by challenging purification our knowledge interactions therefore been restricted PE25–PPE41 pair its with chaperone EspG5. Here, we report crystal structure a new pair, PE8–PPE15, Our revealed that EspG5-binding sites on PPE15 relatively conserved among PPE suggesting EspG5–PPE15 represents more typical model EspG5–PPE than EspG5–PPE41. A structural comparison disclosed conformational changes four-helix bundle binding mode PE8–PPE15 pair. Moreover, homology-modeling mutagenesis studies further delineated molecular determinants These findings help develop an atomic algorithm substrate recognition pairing.