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

香港中文大學研究人員

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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)
會議開始日28.08.2017
會議完結日29.08.2017
會議地點Hong Kong
會議國家/地區香港
出版年份2017
語言美式英語

上次更新時間 2018-23-05 於 12:22