Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin

Leiman, P.G.; Basler, Marek; Ramagopal, U.A.; Bonanno, J.B.; Sauder, J.M.; Pukatzki, Stefan; Burley, S.K.; Almo, Steven C.; Mekalanos, John J.

doi:10.1073/pnas.0813360106

Cited by 580 publications

(680 citation statements)

References 45 publications

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“…The T6SS spike complex is proposed to be formed by a VgrG trimer and a single PAAR protein (Leiman et al , 2009; Shneider et al , 2013). The central spike density has indeed well‐resolved features in the threefold symmetry reconstruction (Appendix Fig S1A).…”

Section: Resultsmentioning

confidence: 99%

“…Evolutionarily related Type VI secretion system (T6SS) is used by bacteria to deliver proteins into both bacterial and eukaryotic cells (Mougous et al , 2006; Pukatzki et al , 2006; Hood et al , 2010; MacIntyre et al , 2010; Durand et al , 2014; Ho et al , 2014; Alcoforado Diniz et al , 2015; Hachani et al , 2016). The current model of T6SS biogenesis and mode of action is largely based on well‐understood phage assembly (Leiman et al , 2009; Lossi et al , 2011, 2013; Ho et al , 2014; Zoued et al , 2014; Clemens et al , 2015; Kudryashev et al , 2015; Cianfanelli et al , 2016). However, many important features are unknown mostly due to the lack of high‐resolution structural information of T6SS.…”

Section: Introductionmentioning

confidence: 99%

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Cryo‐ EM reconstruction of Type VI secretion system baseplate and sheath distal end

et al. 2017

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The bacterial Type VI secretion system (T6SS) assembles from three major parts: a membrane complex that spans inner and outer membranes, a baseplate, and a sheath–tube polymer. The baseplate assembles around a tip complex with associated effectors and connects to the membrane complex by TssK. The baseplate assembly initiates sheath–tube polymerization, which in some organisms requires TssA. Here, we analyzed both ends of isolated non‐contractile Vibrio cholerae sheaths by cryo‐electron microscopy. Our analysis suggests that the baseplate, solved to an average 8.0 Å resolution, is composed of six subunits of TssE/F2/G and the baseplate periphery is decorated by six TssK trimers. The VgrG/PAAR tip complex in the center of the baseplate is surrounded by a cavity, which may accommodate up to ~450 kDa of effector proteins. The distal end of the sheath, resolved to an average 7.5 Å resolution, shows sixfold symmetry; however, its protein composition is unclear. Our structures provide an important step toward an atomic model of the complete T6SS assembly.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cryo‐ EM reconstruction of Type VI secretion system baseplate and sheath distal end

et al. 2017

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“…The bacterial T6SS clearly possesses proteins related to the contractile tail sheath, tube, BW1, BH2, and BS proteins (15), implying that this system is evolutionarily related to phage tails. Given that prophages provide the most abundant source of phage genes that could be adapted for other purposes by their bacterial hosts, it is probable the T6SS originally evolved from a prophage.…”

Section: Defining the Broadly Conserved Components Of The Simple Contmentioning

confidence: 99%

Baseplate assembly of phage Mu: Defining the conserved core components of contractile-tailed phages and related bacterial systems

Buttner

Maxwell

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Contractile phage tails are powerful cell puncturing nanomachines that have been co-opted by bacteria for self-defense against both bacteria and eukaryotic cells. The tail of phage T4 has long served as the paradigm for understanding contractile tail-like systems despite its greater complexity compared with other contractile-tailed phages. Here, we present a detailed investigation of the assembly of a "simple" contractile-tailed phage baseplate, that of Escherichia coli phage Mu. By coexpressing various combinations of putative Mu baseplate proteins, we defined the required components of this baseplate and delineated its assembly pathway. We show that the Mu baseplate is constructed through the independent assembly of wedges that are organized around a central hub complex. The Mu wedges are comprised of only three protein subunits rather than the seven found in the equivalent structure in T4. Through extensive bioinformatic analyses, we found that homologs of the essential components of the Mu baseplate can be identified in the majority of contractile-tailed phages and prophages. No T4-like prophages were identified. The conserved simple baseplate components were also found in contractile tailderived bacterial apparatuses, such as type VI secretion systems, Photorhabdus virulence cassettes, and R-type tailocins. Our work highlights the evolutionary connections and similarities in the biochemical behavior of phage Mu wedge components and the TssF and TssG proteins of the type VI secretion system. In addition, we demonstrate the importance of the Mu baseplate as a model system for understanding bacterial phage tail-derived systems.baseplate | assembly | contractile tail | phage Mu

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“…Functional and structural studies have shown that the T6SS nanomachine shares striking similarities with the bacteriophage tail structure (14)(15)(16)(17)(18)(19)(20)(21)(22). Accumulating evidence suggests that the baseplate complex is recruited into the membrane-associated protein complex and initiates the polymerization of a TssB-TssC (VipAVipB) contractile sheath.…”

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confidence: 99%

VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor–effector complex

Bondage

Lin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Type VI secretion system (T6SS) is a macromolecular machine used by many Gram-negative bacteria to inject effectors/toxins into eukaryotic hosts or prokaryotic competitors for survival and fitness. To date, our knowledge of the molecular determinants and mechanisms underlying the transport of these effectors remains limited. Here, we report that two T6SS encoded valine-glycine repeat protein G (VgrG) paralogs in Agrobacterium tumefaciens C58 specifically control the secretion and interbacterial competition activity of the type VI DNase toxins Tde1 and Tde2. Deletion and domain-swapping analysis identified that the C-terminal extension of VgrG1 specifically confers Tde1 secretion and Tde1-dependent interbacterial competition activity in planta, and the C-terminal variable region of VgrG2 governs this specificity for Tde2. Functional studies of VgrG1 and VgrG2 variants with stepwise deletion of the C terminus revealed that the C-terminal 31 aa (C31) of VgrG1 and 8 aa (C8) of VgrG2 are the molecular determinants specifically required for delivery of each cognate Tde toxin. Further in-depth studies on Tde toxin delivery mechanisms revealed that VgrG1 interacts with the adaptor/chaperone-effector complex (Tap-1-Tde1) in the absence of proline-alanine-alanine-arginine (PAAR) and the VgrG1-PAAR complex forms independent of Tap-1 and Tde1. Importantly, we identified the regions involved in these interactions. Although the entire C31 segment is required for binding with the Tap-1-Tde1 complex, only the first 15 aa of this region are necessary for PAAR binding. These results suggest that the VgrG1 C terminus interacts sequentially or simultaneously with the Tap-1-Tde1 complex and PAAR to govern Tde1 translocation across bacterial membranes and delivery into target cells for antibacterial activity.type VI secretion system | VgrG | DNase effector | interbacterial competition | Agrobacterium tumefaciens

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Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin

Cited by 580 publications

References 45 publications

Cryo‐ EM reconstruction of Type VI secretion system baseplate and sheath distal end

Cryo‐ EM reconstruction of Type VI secretion system baseplate and sheath distal end

Baseplate assembly of phage Mu: Defining the conserved core components of contractile-tailed phages and related bacterial systems

VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor–effector complex

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