PilZ domain

{{Infobox protein family

| Symbol = PilZ

| Name = PilZ

| image = PDB 1ywu EBI.jpg

| width =

| caption = the solution NMR structure of the protein of unknown function vca0042 from vibrio cholerae o1

| Pfam = PF07238

| Pfam_clan =

| InterPro = IPR009875

| SMART =

| PROSITE =

| MEROPS =

| SCOP =

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

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.{{cite journal |vauthors=Alm RA, Bodero AJ, Free PD, Mattick JS | title = Identification of a novel gene, pilZ, essential for type 4 fimbrial biogenesis in Pseudomonas aeruginosa | journal = J. Bacteriol. | volume = 178 | issue = 1 | pages = 46–53 |date=January 1996 | pmid = 8550441 | pmc = 177619 | doi = 10.1128/jb.178.1.46-53.1996}} PilZ is a c-di-GMP binding domain and PilZ domain-containing proteins represent the best studied class of c-di-GMP effectors.{{cite journal|last=Ryjenkov|first=DA|author2=Simm, R |author3=Römling, U |author4= Gomelsky, M |title=The PilZ domain is a receptor for the second messenger c-di-GMP: the PilZ domain protein YcgR controls motility in enterobacteria.|journal=The Journal of Biological Chemistry|date=Oct 13, 2006|volume=281|issue=41|pages=30310–4|pmid=16920715|doi=10.1074/jbc.C600179200|doi-access=free}} C-di-GMP, cyclic diguanosine monophosphate, the second messenger in cells, is widespread in and unique to the bacterial kingdom.{{cite journal|last=Amikam|first=D|author2=Galperin, MY |title=PilZ domain is part of the bacterial c-di-GMP binding protein.|journal=Bioinformatics|date=Jan 1, 2006|volume=22|issue=1|pages=3–6|pmid=16249258|doi=10.1093/bioinformatics/bti739|doi-access=free}} 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.{{cite journal|last=Mattick|first=JS|title=Type IV pili and twitching motility.|journal=Annual Review of Microbiology|year=2002|volume=56|pages=289–314|pmid=12142488|doi=10.1146/annurev.micro.56.012302.160938}}{{cite journal|last=Wolfe|first=AJ|author2=Visick, KL |title=Get the message out: cyclic-Di-GMP regulates multiple levels of flagellum-based motility.|journal=Journal of Bacteriology|date=Jan 2008|volume=190|issue=2|pages=463–75|pmid=17993515|doi=10.1128/JB.01418-07|pmc=2223684}}

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.{{cite journal|last=Paul|first=K|author2=Nieto, V |author3=Carlquist, WC |author4=Blair, DF |author5= Harshey, RM |title=The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a "backstop brake" mechanism.|journal=Molecular Cell|date=Apr 9, 2010|volume=38|issue=1|pages=128–39|pmid=20346719|doi=10.1016/j.molcel.2010.03.001|pmc=2929022}}

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.{{cite journal|last=Benach|first=J |author2=Swaminathan, SS |author3=Tamayo, R |author4=Handelman, SK |author5=Folta-Stogniew, E |author6=Ramos, JE |author7=Forouhar, F |author8=Neely, H |author9=Seetharaman, J |author10=Camilli, A |author11=Hunt, JF|title=The structural basis of cyclic diguanylate signal transduction by PilZ domains.|journal=The EMBO Journal|date=Dec 12, 2007|volume=26|issue=24|pages=5153–66|pmid=18034161|doi=10.1038/sj.emboj.7601918|pmc=2140105}}

The PilZ domain is also implicated in the bacterial pathogenicity of the Lyme disease spirochaete, Borrelia burgdorferi, through its binding partner c-di-GMP.{{cite journal|last=Pitzer|first=JE|author2=Sultan, SZ |author3=Hayakawa, Y |author4=Hobbs, G |author5=Miller, MR |author6= Motaleb, MA |title=Analysis of the Borrelia burgdorferi cyclic-di-GMP-binding protein PlzA reveals a role in motility and virulence.|journal=Infection and Immunity|date=May 2011|volume=79|issue=5|pages=1815–25|pmid=21357718|doi=10.1128/IAI.00075-11|pmc=3088147}}