Structure of a pathogenic type 3 secretion system in action

Radics, J., Konigsmaier, L. & Marlovits, T.C. Nat Struct Mol Biol 21, 82-87 (2014)

Speaker: Jui-Chieh Yin (尹睿婕)                  Time: 15:10~16:00, Apr.23, 2014

Commentator: Dr. Shang-Rung Wu (吳尚蓉老師)    Place: Room 601

Abstract

Type 3 secretion system (T3SS) is widespread among various gram-negative bacterial pathogens such as Shigella flexneri, Salmonella typhimurium, and enteropathogenic Escherichia coli (EPEC).T3SS is a multi-protein needle-like structure and is embedded in the inner and outer membrane of bacteria. It spans the periplasmic space, and utilizes injectisome to translocate number of effector proteins into their respective host organisms.¹ After entering the cytosol of eukaryotic cells, effector proteins make the bacteria more accessible to invade into host and to modulate cellular processes of the host. Currently, structure of T3SS is well-known but the mechanism and conformational changes of the substrates during secretion through injectisome are still unclear. To clarify the structure of substrates within injectisome of S. typhimurium, the authors designed a new set of substrates to test the ability to pass through the injectisome. In this study, they constructed SptP-based tandem-repeat substrates with or without GFP fusion. The GFP-fused substrates were trapped within the needle complex that is allowed to be observed in action and in situ. According to a previously published paper, the chaperone-binding domain of the SptP might be secreted unfolded or partially folded.² The authors used Cryo-EM technique to reveal that the export apparatus ofinjectisomes undergoes only minor conformational changes between substrate-trapped and empty form. Furthermore, they discovered that exogenously expressed substrates competed with natural bacterial effectors for access to secretion machineries. In conclusion, the authors identify that effector proteins need to be unfolded during the process of passing through T3SS. In addition, exogenous substrates might be rejected from injectisomes. This study provides insights into the development of new therapeutic strategies that use substrate analogues to block the entry of secretion pathway to avoid entering of natural bacterial proteins.

References

1.         Tosi, T., Pflug, A., Discola, K.F., Neves, D. & Dessen, A. Structural basis of eukaryotic cell targeting by type III secretion system (T3SS) effectors. Res Microbiol 164, 605-619 (2013)

2.         Stebbins, C.E. & Galan, J.E. Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion. Nature 414, 77-81 (2001)