5xfs
Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosisCrystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis
Structural highlights
Function[ESPG5_MYCTU] Specific chaperone for cognate PE/PPE proteins. Plays an important role in preventing aggregation of PE/PPE dimers.[1] [PPE15_MYCTU] May play a critical role in the homeostasis of triacylglycerol-containing lipid droplets in M.tuberculosis and influence the entry of the pathogen into a dormant state.[2] Publication Abstract from PubMedMycobacterium 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 the PE-PPE family of proteins, which is 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. Structural basis of the PE-PPE protein interaction in Mycobacterium tuberculosis.,Chen X, Cheng HF, Zhou J, Chan CY, Lau KF, Tsui SK, Au SW J Biol Chem. 2017 Oct 13;292(41):16880-16890. doi: 10.1074/jbc.M117.802645. Epub , 2017 Aug 23. PMID:28842489[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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