5XFS

Crystal structure of PE8-PPE15 in complex with EspG5 from M. tuberculosis

Summary for 5XFS

• Entry DOI: 10.2210/pdb5xfs/pdb
• Descriptor: PE family protein PE8, PPE family protein PPE15, ESX-5 secretion-associated protein EspG5, ... (4 entities in total)
• Functional Keywords: tuberculosis, bacterial pathogenesis, protein secretion, protein complex, protein structure, protein transport
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv); More
• Cellular location: Cytoplasm : O53943
• Total number of polymer chains: 3
• Total formula weight: 64114.05

Authors

Chen, X.,Au, S.W.N. (deposition date: 2017-04-11, release date: 2017-08-30, Last modification date: 2023-11-22)

Primary citation

Chen, X.,Cheng, H.F.,Zhou, J.,Chan, C.Y.,Lau, K.F.,Tsui, S.K.,Au, S.W.
Structural basis of the PE-PPE protein interaction in Mycobacterium tuberculosis.
J. Biol. Chem., 292:16880-16890, 2017

PubMed Abstract: (), 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 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 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.

PubMed: 28842489
DOI: 10.1074/jbc.M117.802645

Experimental method

X-RAY DIFFRACTION (2.9 Å)