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Biozentrum : Divide et impera - approach to identify the sole ruler
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Published online 23 July 2010
A well-defined question tackled with a combined investigative approach has led to straightforward interpretation: the length of the injectisome needle from Yersinia is controlled by just one molecular ruler protein YscP. This conclusion of Guy Cornelis’ group was made possible with a combined genetic and mathematical modeling approach against the backdrop of a general interest in the assembly mechanisms of virulence nanomachines.
The determination of the size of a molecular structure, such as the length of the injection apparatus found in pathogenic bacteria, is a fundamental biological problem and is only recently on the verge of being understood. The bacterial injectisome or needle complex allows pathogenic bacteria to inject bacterial proteins across eukaryotic cell membranes, a process called type III secretion (T3S). For example, the T3S injectisome of Yersinia enterocolitica is a nanosyringe composed of a basal body, an export apparatus and a 65 nm long stiff hollow needle. This needle is composed of about 140 copies of the 9 kDa YscF protein and its length is controlled by the Yop secretion protein P (YscP). Moreover, a direct correlation between the length of the needle and the length of the molecular ruler YscP was observed. But how exactly does the interplay between YscF proteins and length controlling YscP proteins in a growing needle look like? To address this question and to be able to distinguish between different scenarios of length control, one needs to know how many molecular ruler proteins are necessary to control the length of one injectisome needle.
In a combined effort, the labs of Guy Cornelis (Biozentrum, University of Basel) and Matteo Dal Peraro (EPFL) have applied a genetic and mathematical modeling approach to address this question. In a current article in PNAS, they show that only one single molecule of YscP is required to control the length of one needle. These findings are only compatible with the so-called “static ruler model”: To act as a molecular ruler YscP would enter the channel of the growing needle, monitor needle lenght during assembly and stop export of YscF – the needle’s building blocks - when the correct needle length is reached. The results, however, disfavor the “dynamic ruler model” where the elongation of each needle is controlled by multiple rulers or “tape-measure molecules” that keep passing through and eventually stop needle growth.
The group of Cornelis genetically engineered three different strains of Y. entereocolitica simultaneously expressing a short and a long version of YscP and analyzed the needle length distribution by transmission electron microscopy. The experimental data, statistically analyzed and compared to the predictions from stochastic modeling of various possible scenarios are perfectly in line with the single ruler model but not with scenarios involving more than one ruler per needle.
Understanding type III secretion and needle length control in greater detail would allow the design of therapeutic drugs, which would selectively and specifically disarm pathogenic bacteria carrying the nanosyringe weapon, and allow our white blood cells to engulf and eliminate them.
Source article
Wagner, S., Stenta, M., Metzger, L. C., Dal Peraro, M. & Cornelis, G. R. 2010. Length control of the injectisome needle requires only one molecule of Yop secretion protein P (YscP). PNAS published ahead of print July 19, 2010, doi:10.1073/pnas.1006985107. Download
Source: Biozentrum
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