6UUJ

Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group P212121

Summary for 6UUJ

• Entry DOI: 10.2210/pdb6uuj/pdb
• Related: 6VHR
• Descriptor: PE family immunomodulator PE5, PPE family protein PPE4, ESX-3 secretion-associated protein EspG3, ... (4 entities in total)
• Functional Keywords: chaperone, protein secretion, protein transport
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv); More
• Total number of polymer chains: 12
• Total formula weight: 232814.12

Authors

Williamson, Z.A.,Korotkov, K.V. (deposition date: 2019-10-30, release date: 2020-01-29, Last modification date: 2023-10-11)

Primary citation

Williamson, Z.A.,Chaton, C.T.,Ciocca, W.A.,Korotkova, N.,Korotkov, K.V.
PE5-PPE4-EspG3heterotrimer structure from mycobacterial ESX-3 secretion system gives insight into cognate substrate recognition by ESX systems.
J.Biol.Chem., 295:12706-12715, 2020

PubMed Abstract: has evolved numerous type VII secretion (ESX) systems to secrete multiple factors important for both growth and virulence across their cell envelope. ESX-1, ESX-3, and ESX-5 systems have been shown to each secrete a distinct set of substrates, including PE and PPE families of proteins, named for conserved Pro-Glu and Pro-Pro-Glu motifs in their N termini. Proper secretion of the PE-PPE proteins requires the presence of EspG, with each system encoding its own unique copy. There is no cross-talk between any of the ESX systems, and how each EspG recognizes its subset of PE-PPE proteins is currently unknown. The only current structural characterization of PE-PPE-EspG heterotrimers is from the ESX-5 system. Here we present the crystal structure of the PE5-PPE4-EspG heterotrimer from the ESX-3 system. Our heterotrimer reveals that EspG interacts exclusively with PPE4 in a similar manner to EspG, shielding the hydrophobic tip of PPE4 from solvent. The C-terminal helical domain of EspG is dynamic, alternating between "open" and "closed" forms, and this movement is likely functionally relevant in the unloading of PE-PPE heterodimers at the secretion machinery. In contrast to the previously solved ESX-5 heterotrimers, the PE-PPE heterodimer of our ESX-3 heterotrimer is interacting with its chaperone at a drastically different angle and presents different faces of the PPE protein to the chaperone. We conclude that the PPE-EspG interface from each ESX system has a unique shape complementarity that allows each EspG to discriminate among noncognate PE-PPE pairs.

PubMed: 32675282
DOI: 10.1074/jbc.RA120.012698

Experimental method

X-RAY DIFFRACTION (3 Å)