![]() However, in all structures known to date, the proposed translocation channel through the EA is sealed by a gasket with an above loop, making comprehension of substrate transport through the needle complex difficult. The basal body and the needle filament, collectively termed the needle complex, function as a continuous conduit for effector protein translocation from the prokaryotic to the host cell cytoplasm 10, 11.Īccumulating structural information has revealed a shared common architecture between injectisome and flagellar T3SSs, especially in the EA 6, 12, 13, 14, 15. Extending from the EA is a long, helical needle filament, capped by a tip complex that contacts the host cell membrane via assembly of a translocon pore 7, 8, 9. Chaperones present effector proteins in a non-globular, secretion-competent state to a cytoplasmic sorting platform complex, which sorts and loads effectors into the export apparatus (EA) subcomplex located inside the membrane-bound basal body 3, 4, 5, 6. The injectisome is a large molecular machine, over 3.6 MDa in mass, spanning across the inner and outer bacterial membranes with an extracellular filamentous appendage extending out to target host cells. Therefore, visualizing the translocation process at the molecular level is essential for our understanding of host–pathogen biology and the development of novel therapies targeting bacterial infection. Yet, the precise mechanisms that allow these secretion systems to facilitate unfolded protein transport across the bacterial envelope and into the host cell while maintaining bacterial membrane remain integrity poorly understood. These proteins modulate host cell signal transduction processes to establish a biological niche within the host, making T3SSs crucial virulence determinants 2. Many important human pathogens including Salmonella, Shigella, Yersinia, and enteropathogenic Escherichia coli employ a conserved, virulent type III secretion system (T3SS), also commonly referred to as the injectisome, to deliver a pleiotropic arsenal of proteins into target eukaryotic cells 1. Together, these findings establish the molecular basis for substrate translocation through T3SSs and improve our understanding of bacterial pathogenicity and motility. Following gate penetration, a moveable SpaR loop first folds up to then support substrate transport. Above, a methionine gasket formed by SpaP proteins functions as a gate that dilates to accommodate substrates while preventing leaky pore formation. Unfolded substrates enter the EA through a hydrophilic constriction formed by SpaQ proteins, which enables side chain-independent substrate transport. 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 800Å-long secretion conduit and unraveling the critical role of the export apparatus (EA) subcomplex in type III secretion. However, the molecular principles underlying type III secretion remain elusive. ![]() 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. Many bacterial pathogens rely on virulent type III secretion systems (T3SSs) or injectisomes to translocate effector proteins in order to establish infection.
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