Cryo-EM analysis of the T3S injectisome reveals the structure of the needle and open secretin

Jin-hong, HU; Worrall, L.J.; Hong, Chuan; Vuckovic, M.; Atkinson, Claire; Caveney, Nathanael; Yu, Zhiheng; Strynadka, N.C.J.

doi:10.1038/s41467-018-06298-8

Cited by 110 publications

(160 citation statements)

References 60 publications

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“…A remarkable characteristic of this system is the needle complex that encompasses both inner and outer membrane rings and is completed by a protruding hollow needle. This apparatus allows the passage of substrates in semiunfolded form into the eukaryotic cytoplasm through a pore formed directly on the target cell membrane, thus forming a direct channel between the bacterial cytoplasm and that of the host …”

Section: Assembly Of T3ss Secretinsmentioning

confidence: 99%

“…N0 in EpsD from the T2SS of V. vulnificus was not traceable in the cryo‐EM map due to flexibility and is thus indicated in blue. Numbers indicate domain delimitations, as indicated in the publications describing the structures in Figure …”

Section: Introductionmentioning

confidence: 99%

“…Cryo‐EM structures of secretins (T2SS, T4PS) and injectisome needle complex (T3SS). The resolution of the maps for the T2SS (EpsD from V. vulnificus , 3.4 Å) and T3SS (InvG, PrgH, PrgK, PrgI from S. typhimurium ; ~3.6 Å) allowed for the positioning of the monomer (orange) including the S‐domain (red). The T3SS needle is indicated in cyan.…”

Section: Introductionmentioning

confidence: 99%

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Bacterial secretins: Mechanisms of assembly and membrane targeting

et al. 2020

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Secretion systems are employed by bacteria to transport macromolecules across membranes without compromising their integrities. Processes including virulence, colonization, and motility are highly dependent on the secretion of effector molecules toward the immediate cellular environment, and in some cases, into the host cytoplasm. In Type II and Type III secretion systems, as well as in Type IV pili, homomultimeric complexes known as secretins form large pores in the outer bacterial membrane, and the localization and assembly of such 1 MDa molecules often relies on pilotins or accessory proteins. Significant progress has been made toward understanding details of interactions between secretins and their partner proteins using approaches ranging from bacterial genetics to cryo electron microscopy. This review provides an overview of the mode of action of pilotins and accessory proteins for T2SS, T3SS, and T4PS secretins, highlighting recent near‐atomic resolution cryo‐EM secretin complex structures and underlining the importance of these interactions for secretin functionality.

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Section: Assembly Of T3ss Secretinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bacterial secretins: Mechanisms of assembly and membrane targeting

et al. 2020

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“…Currently, the atomic structures of the assembled needles (Figure a) are only available for Salmonella and Shigella needles of the Inv‐Mxi‐Spa family of T3SS . The atomic structure of the assembled needle for any of the Ysc family remains unknown.…”

Section: Structure Of the Assembled Needles And Needle Monomersmentioning

confidence: 99%

“…The atomic structure of the assembled needle for any of the Ysc family remains unknown. The needle has nanoscale dimensions of ~50 nm long, ~7 nm wide, and a lumen diameter from 1.5 nm to 2.5 nm Electron microscopy of partially purified needles from P. aeruginosa showed structures that were 60–80 nm long and 6–8 nm wide . The needle is assembled from the polymerization of many copies of a small needle protein of about 80 residues, and arranged in a helical symmetry along the needle axis.…”

Section: Structure Of the Assembled Needles And Needle Monomersmentioning

confidence: 99%

The type III secretion system needle, tip, and translocon

et al. 2019

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Many Gram‐negative bacteria pathogenic to plants and animals deploy the type III secretion system (T3SS) to inject virulence factors into their hosts. All bacteria that rely on the T3SS to cause infectious diseases in humans have developed antibiotic resistance. The T3SS is an attractive target for developing new antibiotics because it is essential in virulence, and part of its structural component is exposed on the bacterial surface. The structural component of the T3SS is the needle apparatus, which is assembled from over 20 different proteins and consists of a base, an extracellular needle, a tip, and a translocon. This review summarizes the current knowledge on the structure and assembly of the needle, tip, and translocon.

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Integrative structural analysis of the type III secretion system needle complex from Shigella flexneri

et al. 2023

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The type III secretion system (T3SS) is a large, transmembrane protein machinery used by various pathogenic gram‐negative bacteria to transport virulence factors into the host cell during infection. Understanding the structure of T3SSs is crucial for future developments of therapeutics that could target this system. However, much of the knowledge about the structure of T3SS is available only for Salmonella, and it is unclear how this large assembly is conserved across species. Here, we combined cryo‐electron microscopy, cross‐linking mass spectrometry, and integrative modeling to determine the structure of the T3SS needle complex from Shigella flexneri. We show that the Shigella T3SS exhibits unique features distinguishing it from other structurally characterized T3SSs. The secretin pore complex adopts a new fold of its C‐terminal S domain and the pilotin MxiM[SctG] locates around the outer surface of the pore. The export apparatus structure exhibits a conserved pseudohelical arrangement but includes the N‐terminal domain of the SpaS[SctU] subunit, which was not present in any of the previously published virulence‐related T3SS structures. Similar to other T3SSs, however, the apparatus is anchored within the needle complex by a network of flexible linkers that either adjust conformation to connect to equivalent patches on the secretin oligomer or bind distinct surface patches at the same height of the export apparatus. The conserved and unique features delineated by our analysis highlight the necessity to analyze T3SS in a species‐specific manner, in order to fully understand the underlying molecular mechanisms of these systems. The structure of the type III secretion system from Shigella flexneri delineates conserved and unique features, which could be used for the development of broad‐range therapeutics.

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Cryo-EM analysis of the T3S injectisome reveals the structure of the needle and open secretin

Cited by 110 publications

References 60 publications

Bacterial secretins: Mechanisms of assembly and membrane targeting

Bacterial secretins: Mechanisms of assembly and membrane targeting

The type III secretion system needle, tip, and translocon

Integrative structural analysis of the type III secretion system needle complex from Shigella flexneri

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