Featured System - August 2014
Short description: PSI researchers have determined the structure of a transcriptional regulator involved in quorum sensing in an important pathogenic bacterium.
There is power in numbers, and bacteria take advantage of this by cooperating with their neighbors to colonize an environment. In a process called "quorum sensing," bacteria communicate with one another, making decisions as a group about the optimal type of growth. For instance, several strains of opportunistic bacteria use this process to create biofilms when they find a susceptible host, switching from an individual, exploratory mode of living to a group effort that forms a tough, resilient film. This can have deadly consequences for the host, since these biofilms are difficult to fight.
Quorum sensing relies on communication between neighbors, so that they can make decisions together. The bacteria communicate by releasing small signaling molecules, which are picked up by their neighbors. The system can be quite simple, relying primarily on two proteins. One protein generates the signaling molecules, which are released into the environment. When the levels of these molecules reach a critical amount (because the cells are getting crowded), the other protein receives the signal and turns on hundreds of genes involved in, for instance, the formation of biofilms and other molecules important for virulence.
Many types of bacteria use a combination of a serine and a fatty acid, termed a N-acyl homoserine lactone (AHL), as their signal. These molecules are perfect for the task because they are easily created from molecules normally made by the cell and they readily pass in and out of cells. Also, by using different types of fatty acids, unique variants of these molecules can be crafted by different strains of bacteria, so they are able to communicate with only their kin. The two proteins shown here are involved in quorum sensing with AHL: an AHL synthase on the top (PDB entry 1ro5) and an AHL-binding transcription factor at the bottom (PDB entry 1l3l).
PSI researchers at MCSG have recently explored a refinement of the process of quorum sensing in Burkholderia bacteria, which cause a particularly dangerous form of pneumonia in people with cystic fibrosis. They have solved the structure of a small protein that is encoded in the bacterial genome between the genes for the synthase and the transcription factor, which helps to tune the process (PDB entry 4o2h). The structure revealed an unusual fold and interesting cluster of tryptophan amino acids that stabilize the structure. Comparison of the structure with similar proteins also revealed that it most likely does not bind to DNA, so it doesn't appear to regulate genes directly. So, there still are some mysteries to be solved about how it exerts its regulatory effects. To explore this new protein structure in more detail, the JSmol tab below displays an interactive JSmol.
The structure of RsaM revealed a new protein fold composed of a beta sheet wrapped around a kinked alpha helix. A cluster of four tryptophan amino acids forms a carbon-rich core that stabilizes each chain. The protein forms a dimer in solution, and the crystal lattice included several different ways that each chain interacted with its neighbors. The dimer with the largest surface of interaction in the crystal is shown here. Use the buttons to display the tryptophan core and to change the way the protein is represented and colored.
Michalska, K. et al. RsaM - a transcriptional regulator of Burkholderia spp. with novel fold. FEBS J. 2014 (epub ahead of print).
Rutherford, S. T. & Bassler, B. L. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harbor Persp. Med. 2:a012427 (2012).
Gould, T. A., Schweizer, H. P. & Churchill, M. E. A. Structure of the Pseudomonas aeruginosa acyl-homoserinelactone synthase LasI. Mol. Microbio. 53, 1135-1146 (2004).
Zhang, R. G. et al. Structure of a bacterial quorum-sensing transcription factor complexed with pheromone and DNA. Nature 417, 971-974 (2002).