Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion
- Univ. of California, San Francisco, CA (United States). Dept. Microbiology and Immunology
Nearly 10% of the coding capacity of the Mycobacterium tuberculosis genome is devoted to two highly expanded and enigmatic protein families called PE and PPE, some of which are important virulence/immunogenicity factors and are secreted during infection via a unique alternative secretory system termed "type VII." How PE-PPE proteins function during infection and how they are translocated to the bacterial surface through the five distinct type VII secretion systems [ESAT-6 secretion system (ESX)] of M. tuberculosis is poorly understood. Here in this paper, we report the crystal structure of a PE-PPE heterodimer bound to ESX secretion-associated protein G (EspG), which adopts a novel fold. This PE-PPE-EspG complex, along with structures of two additional EspGs, suggests that EspG acts as an adaptor that recognizes specific PE-PPE protein complexes via extensive interactions with PPE domains, and delivers them to ESX machinery for secretion. Surprisingly, secretion of most PE-PPE proteins in M. tuberculosis is likely mediated by EspG from the ESX-5 system, underscoring the importance of ESX-5 in mycobacterial pathogenesis. Furthermore, our results indicate that PE-PPE domains function as cis-acting targeting sequences that are read out by EspGs, revealing the molecular specificity for secretion through distinct ESX pathways.
- Research Organization:
- Univ. of California, San Francisco, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Damon Runyon Cancer Research Foundation
- Grant/Contract Number:
- AC02-05CH11231; R01AI081727; DRG-2140-12
- OSTI ID:
- 1347686
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, Issue 41; ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)Copyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
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