Featured System - April 2012
Short description: Many bacteria are covered with long filaments, called pili or fimbriae, that help them interact and attach to their environment.
Many bacteria are covered with long filaments, called pili or fimbriae, that help them interact and attach to their environment. Typically the genomes of these bacteria have a large locus of genes that encode proteins for the synthesis, localization and assembly of these filaments. As part of a community-nominated project, JCSG researchers have solved the structure of one of these proteins, TadZ (PDB entry 3fkq), and from it, discovered its function.
Pili come in several shapes and sizes. The ones shown here on the left, extending from the surface of an Escherichia coli cell, are termed "type I" pili. They are built using a complex usher system that guides subunits to the surface, assembles them, and pushes them out through a narrow pore in the cell surface. The pilin subunit on the right (PDB entry 1ay2) is different, termed "type IV" pilin, which is built using an ATP-driven motor and a large circular pore. Pilin proteins have a characteristic shape, with a globular domain that forms the outer surface of the fiber, and a long hydrophic tail that packs into the middle of the fiber. This unique structure forms a filament that is very narrow, but also extremely strong.
Understanding of pilus form and function is important, since pili play central roles in many pathogenic bacteria. For instance, the pili of the bacterium Aggregatibacter actinomycetemcomitans are essential for their adhesion to teeth. They form tenacious biofilms on the surface of teeth, which can lead to periodontal disease. Hopefully, greater understanding of the mechanisms of this adhesion will allow us to develop effective treatments to remove the bacteria.
Biochemical studies have shown that TadZ is important for the localization of pili to the poles of these bacteria, which is required for biofilm formation. Comparison of TadZ with similar proteins provides clues for how this might happen. The protein is composed of two domains. The smaller domain is very similar to signaling proteins like CheY, which use protein-protein interactions to transmit cellular information. TadZ, however, is missing some of the key elements used in this signaling, such as the ability to bind to magnesium and a key aspartate amino acid that is phosphorylated. The large domain is similar to several proteins that cleave ATP in their function. TadZ has a similar ATP binding site--in fact, ATP was serendipitously found in the crystal structure, presumably carried along during the entire process of purification of the protein. However, TadZ cleaves ATP more slowly, so JCSG researchers now see TadZ as a molecular hub, using its protein-binding domain to recruit other pilus-constructing proteins, and using ATP to strengthen the connection between its two subunits. To explore these structures in more detail, the JSmol tab below displays an interactive JSmol.
The two TadZ domains are compared to two proteins with similar folds (use the buttons to display them). The smaller domain is similar to other protein-protein signaling proteins like CheY. However, CheY has a special aspartate that gets phosphorylated (shown in green) and it binds to a magnesium ion (in yellow), both of which are important in its function and are not present in TadZ. The larger domain is similar to ATPases like Soj. However, the ATP-binding site of TadZ has lost some important m
Xu, Q. et al. Structure of the pilus assembly protein TadZ from Eubacterium rectale: implications for polar localization. Mol. Microbiol. 83, 712-727 (2012).
Perez-Cheeks, B. A. et al. The product of TadZ, a new member of the parA/minD superfamily, localizes to a pole in Aggregatibacter actinomycetemcomitans. Mol. Microbiol. 83, 694-711 (2012).
Proft, T. & Baker, E. N. Pili in gram-negative and gram-positive bacteria -- structure, assembly and their role in disease. Cell. Mol. Life Sci. 66, 613-635 (2009).
Craig, L., Pique, M. E. & Tainer, J. A. Type IV pilus structure and bacterial pathogenicity. Nat. Rev. Microbio. 2, 363-378 (2004).
3fkq - Xu, Q. et al. Structure of the pilus assembly protein TadZ from Eubacterium rectale: implications for polar localization. Mol. Microbiol. 83, 712-727 (2012).
2bek - Leonard, T. A., Butler, P. J. & Lowe, J. Bacterial chromosome segregation: structure and DNA binding of Soj dimer--a conserved biological switch. EMBO J. 24, 270-282 (2005).
1ay2 - Parge, H. E., Forest, K. T., Hickey, M. J., Christensen, D. A., Getzoff, E. D. & Tainer, J. A. Structure of the fibre-forming protein pilin at 2.6 A resolution. Nature 378, 32-38 (1995).
2che - Stock, A. M. et al. Structure of the Mg(2+)-bound form of CheY and mechanism of phosphoryl transfer in bacterial chemotaxis. Biochemistry 32, 13375-13380 (1993).