Structural basis of PE-PPE protein interaction in Mycobacterium tuberculosis
Invited conference paper presented and published in conference proceedings



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

上次更新時間 2018-23-05 於 12:22