Substrate-engaged type III secretion system structures reveal gating mechanism for unfolded protein translocation
| Autor: | Vadim Kotov, Dirk Fahrenkamp, Maurice Pantel, Nikolaus Goessweiner-Mohr, Oliver Vesper, Thomas C. Marlovits, Jiri Wald, Sean Miletic |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation alpha-Helical Salmonella typhimurium Science General Physics and Astronomy Virulence General Biochemistry Genetics and Molecular Biology Article Type three secretion system 03 medical and health sciences 0302 clinical medicine Bacterial secretion Bacterial Proteins Type III Secretion Systems Secretion Host cell membrane Antigens Bacterial Multidisciplinary Chemistry Effector Cryoelectron Microscopy Membrane Proteins Salmonella enterica Biological membrane General Chemistry Cell biology Protein Transport 030104 developmental biology Membrane protein Host cell cytoplasm ddc:500 Signal transduction Cell envelope Pathogens 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) Nature Communications 12(1), 1546 (2021). doi:10.1038/s41467-021-21143-1 Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Nature Communications 12(1), 1546 (2021). doi:10.1038/s41467-021-21143-1 Many bacterial pathogens rely on virulent type III secretion systems (T3SSs) or injectisomes to translocate effector proteins in order to establish infection. The central component of the injectisome is the needle complex which assembles a continuous conduit crossing the bacterial envelope and the host cell membrane to mediate effector protein translocation. However, the molecular principles underlying type III secretion remain elusive. Here, we report a structure of an active Salmonella enterica serovar Typhimurium needle complex engaged with the effector protein SptP in two functional states, revealing the complete 800��-long secretion conduit and unraveling the critical role of the export apparatus (EA) subcomplex in type III secretion. Unfolded substrates enter the EA through a hydrophilic constriction formed by SpaQ proteins, which enables side chain-independent substrate transport. Above, a methionine gasket formed by SpaP proteins functions as a gate that dilates to accommodate substrates while preventing leaky pore formation. Following gate penetration, a moveable SpaR loop first folds up to then support substrate transport. Together, these findings establish the molecular basis for substrate translocation through T3SSs and improve our understanding of bacterial pathogenicity and motility. Published by Nature Publishing Group UK, [London] |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink