PilZ domain explained

Symbol:	PilZ
PilZ
Pfam:	PF07238
Interpro:	IPR009875

The PilZ protein family is named after the type IV pilus control protein first identified in Pseudomonas aeruginosa, expressed as part of the pil operon. It has a cytoplasmic location and is essential for type IV fimbrial, or pilus, biogenesis.^[1] PilZ is a c-di-GMP binding domain and PilZ domain-containing proteins represent the best studied class of c-di-GMP effectors.^[2] C-di-GMP, cyclic diguanosine monophosphate, the second messenger in cells, is widespread in and unique to the bacterial kingdom.^[3] Elevated intracellular levels of c-di-GMP generally cause bacteria to change from a motile single-cell state to a sessile, adhesive surface-attached multicellular state called biofilm.^{[4] [5]}

Proteins which contain PilZ are known to interact with the flagellar switch-complex proteins FliG and FliM and this is mediated via the c-di-GMP-PliZ complex. This interaction results in a reduction of torque-generation and induces counterclockwise motor bias that slows the motor and induces counterclockwise rotation, inhibiting chemotaxis.^[6]

Binding and mutagenesis studies of several PilZ domain proteins have shown that c-di-GMP binding depends on residues in RxxxR and D/NxSxxG sequence-motifs. The crystal structure, at 1.7 A, of a PilZ domain::c-di-GMP complex from Vibrio cholerae shows c-di-GMP contacting seven of nine strongly conserved residues. Binding of c-di-GMP causes a conformational switch whereby the C- and N-terminal domains are brought into close opposition forming a new allosteric interaction surface that spans these domains and the c-di-GMP at their interface.^[7]

The PilZ domain is also implicated in the bacterial pathogenicity of the Lyme disease spirochaete, Borrelia burgdorferi, through its binding partner c-di-GMP.^[8]

Notes and References

1. Alm RA, Bodero AJ, Free PD, Mattick JS . Identification of a novel gene, pilZ, essential for type 4 fimbrial biogenesis in Pseudomonas aeruginosa . J. Bacteriol. . 178 . 1 . 46–53 . January 1996 . 8550441 . 177619 . 10.1128/jb.178.1.46-53.1996.
2. Ryjenkov. DA. Simm, R . Römling, U . Gomelsky, M . The PilZ domain is a receptor for the second messenger c-di-GMP: the PilZ domain protein YcgR controls motility in enterobacteria.. The Journal of Biological Chemistry. Oct 13, 2006. 281. 41. 30310–4. 16920715. 10.1074/jbc.C600179200. free.
3. Amikam. D. Galperin, MY . PilZ domain is part of the bacterial c-di-GMP binding protein.. Bioinformatics. Jan 1, 2006. 22. 1. 3–6. 16249258. 10.1093/bioinformatics/bti739. free.
4. Mattick. JS. Type IV pili and twitching motility.. Annual Review of Microbiology. 2002. 56. 289–314. 12142488. 10.1146/annurev.micro.56.012302.160938.
5. Wolfe. AJ. Visick, KL . Get the message out: cyclic-Di-GMP regulates multiple levels of flagellum-based motility.. Journal of Bacteriology. Jan 2008. 190. 2. 463–75. 17993515. 10.1128/JB.01418-07. 2223684.
6. Paul. K. Nieto, V . Carlquist, WC . Blair, DF . Harshey, RM . The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a "backstop brake" mechanism.. Molecular Cell. Apr 9, 2010. 38. 1. 128–39. 20346719. 10.1016/j.molcel.2010.03.001. 2929022.
7. Benach. J . Swaminathan, SS . Tamayo, R . Handelman, SK . Folta-Stogniew, E . Ramos, JE . Forouhar, F . Neely, H . Seetharaman, J . Camilli, A . Hunt, JF. The structural basis of cyclic diguanylate signal transduction by PilZ domains.. The EMBO Journal. Dec 12, 2007. 26. 24. 5153–66. 18034161. 10.1038/sj.emboj.7601918. 2140105.
8. Pitzer. JE. Sultan, SZ . Hayakawa, Y . Hobbs, G . Miller, MR . Motaleb, MA . Analysis of the Borrelia burgdorferi cyclic-di-GMP-binding protein PlzA reveals a role in motility and virulence.. Infection and Immunity. May 2011. 79. 5. 1815–25. 21357718. 10.1128/IAI.00075-11. 3088147.