Molecular ruler determines needle length for the
            <i>Salmonella</i>
            Spi-1 injectisome

Wee, Daniel H.; Hughes, Kelly T.

doi:10.1073/pnas.1423492112

Cited by 33 publications

(36 citation statements)

References 55 publications

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“…Indeed, our crosslinking analysis shows that deletion of SctP as well as mutations previously implicated to interfere with needle length control have no effect on assembly of the inner rod onto SctR and SctT. Thus, it is likely that the alternative needle length control model involving SctP as an infrequently secreted molecular ruler also applies to the SPI-1 T3SS of Salmonella Typhimurium (Journet et al, 2003;Erhardt et al, 2011;Wee and Hughes, 2015).…”

Section: Discussionmentioning

confidence: 73%

The inner rod of virulence‐associated type III secretion systems constitutes a needle adapter of one helical turn that is deeply integrated into the system's export apparatus

Torres-Vargas

Kronenberger

Roos

et al. 2019

Molecular Microbiology

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Summary Type III secretion injectisomes are essential virulence factors for many pathogenic bacteria by mediating the transport of effector proteins into eukaryotic host cells. The secretion conduit of injectisomes is formed by a helical assembly of three hydrophobic proteins (SctR, SctS and SctT), an inner rod (SctI) and a needle filament (SctF). SctI is thought to play a role in switching between the secretion of different substrate classes and assembly of the inner rod has been implicated in regulating the length of the needle filament. While high‐resolution structures of the hydrophobic components and of the needle filament have been solved, little is known about the structure and the assembly of the inner rod, which impedes the deeper assessment of its function. Here we show by exhaustive in vivo photocrosslinking that SctI engages in extensive interactions with SctR and SctT throughout its entire length. Our data imply that the inner rod serves as an adapter between the export apparatus and the needle filament by forming one helical turn. We show that assembly of the inner rod does not play a role in needle length control nor in substrate specificity switching. Instead, our findings imply that inner rod assembly must precede assembly of the needle filament.

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Section: Discussionmentioning

confidence: 73%

The inner rod of virulence‐associated type III secretion systems constitutes a needle adapter of one helical turn that is deeply integrated into the system's export apparatus

Torres-Vargas

Kronenberger

Roos

et al. 2019

Molecular Microbiology

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“…We note, however, that for InvJ and Spa32, the theoretical length of the LS domain does not match with that of the T3SS needle (68,69), taking into account the periplasmic and cytoplasmic space (ϳ70 nm, see Table 2). This could, however, be caused by an excessive estimate of the predicted helical content (56%), because a small decrease to 35% helical would allow the ruler to reach a length of 70 nm.…”

mentioning

confidence: 88%

The Structure of a Type 3 Secretion System (T3SS) Ruler Protein Suggests a Molecular Mechanism for Needle Length Sensing

Bergeron¹,

Fernández

Wasney³

et al. 2016

Journal of Biological Chemistry

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The type 3 secretion system (T3SS) and the bacterial flagellum are related pathogenicity-associated appendages found at the surface of many disease-causing bacteria. These appendages consist of long tubular structures that protrude away from the bacterial surface to interact with the host cell and/or promote motility. A proposed "ruler" protein tightly regulates the length of both the T3SS and the flagellum, but the molecular basis for this length control has remained poorly characterized and controversial. Using the Pseudomonas aeruginosa T3SS as a model system, we report the first structure of a T3SS ruler protein, revealing a "ball-and-chain" architecture, with a globular C-terminal domain (the ball) preceded by a long intrinsically disordered N-terminal polypeptide chain. The dimensions and stability of the globular domain do not support its potential passage through the inner lumen of the T3SS needle. We further demonstrate that a conserved motif at the N terminus of the ruler protein interacts with the T3SS autoprotease in the cytosolic side. Collectively, these data suggest a potential mechanism for needle length sensing by ruler proteins, whereby upon T3SS needle assembly, the ruler protein's N-terminal end is anchored on the cytosolic side, with the globular domain located on the extracellular end of the growing needle. Sequence analysis of T3SS and flagellar ruler proteins shows that this mechanism is probably conserved across systems.

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“…Our initial model, in which the measurement of these structures takes place deterministically with the help of an exact ruler, predicts that variance should be independent of needle length and depend only on number of ruler and needle proteins in the bacterial cell. Our analysis of experimental studies in which the authors obtained length distributions of these structures for a wide range of ruler lengths revealed a linear relatiosnhip between the variance and the average length [10][11][12]. A more realistic approximation of our model, where we introduce uncertainty in the measurement process by the ruler protein, results in a linear relationship between the variance in needles and the average needle lengths if the average length is increased by simply inserting additional amino acid residues to the ruler protein, which is what is done experimentally.…”

mentioning

confidence: 83%

“…Furthermore, there is recent experimental evidence for the length control via the ruler mechanism in Salmonella injectisome, leading to an ongoing controversy about the functions of some of the proteins involved in assembly [12]. Experimental evidence for the ruler mechanism has primarily been provided by demonstrating that the average length of the needles/hooks increases linearly with increases in the length of the ruler protein itself.…”

mentioning

confidence: 99%

Robustness and the evolution of length control strategies in the type III secretion system and flagellar hook

Nariya

Mallela

Shi

et al. 2019

Preprint

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Bacteria construct many structures, like the flagellar hook and the type III secretion system, that aid in crucial processes such as locomotion and pathogenesis. Experimental work has suggested two competing mechanisms bacteria could use to regulate length in these structures: the "ruler" mechanism and the "substrate switching" mechanism. In this work, we constructed a mathematical model of length control based on the ruler mechanism, and found that the predictions of this model are consistent with experimental data not just for the scaling of the average length with the ruler protein length, but also the variance. Interestingly, we found that the ruler mechanism allows for the evolution of needles with large average lengths without the concomitant large increase in variance that occurs in the substrate switching mechanism. These findings shed new light on the trade-offs that may have lead to the evolution of different length control mechanisms in different bacterial species. Length regulation in bacteriaBacterial cells build a variety of structures on their exterior, e.g. flagella, pili, the Type III Secretion System (T3SS), etc., which help to carry out important functions such as locomotion, DNA transfer and pathogenesis [1]. In order to ensure effective function and to optimize the efficiency of transport, bacteria need to control the length of these structures with high precision. This poses a natural question about the regulation of the assembly process: how does the bacterial cell "know" when to stop † Current affiliation:

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Molecular ruler determines needle length for the Salmonella Spi-1 injectisome

Cited by 33 publications

References 55 publications

The inner rod of virulence‐associated type III secretion systems constitutes a needle adapter of one helical turn that is deeply integrated into the system's export apparatus

The inner rod of virulence‐associated type III secretion systems constitutes a needle adapter of one helical turn that is deeply integrated into the system's export apparatus

The Structure of a Type 3 Secretion System (T3SS) Ruler Protein Suggests a Molecular Mechanism for Needle Length Sensing

Robustness and the evolution of length control strategies in the type III secretion system and flagellar hook

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