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42  structures 3357  species 6  interactions 13164  sequences 221  architectures

Family: PilZ (PF07238)

Summary: PilZ domain

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This is the Wikipedia entry entitled "PilZ domain". More...

PilZ domain Edit Wikipedia article

PilZ
PDB 1ywu EBI.jpg
the solution NMR structure of the protein of unknown function vca0042 from vibrio cholerae o1
Identifiers
SymbolPilZ
PfamPF07238
InterProIPR009875

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]

References

  1. ^ Alm RA, Bodero AJ, Free PD, Mattick JS (January 1996). "Identification of a novel gene, pilZ, essential for type 4 fimbrial biogenesis in Pseudomonas aeruginosa". J. Bacteriol. 178 (1): 46–53. PMC 177619. PMID 8550441.
  2. ^ Ryjenkov, DA; Simm, R; Römling, U; Gomelsky, M (Oct 13, 2006). "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. 281 (41): 30310–4. doi:10.1074/jbc.C600179200. PMID 16920715.
  3. ^ Amikam, D; Galperin, MY (Jan 1, 2006). "PilZ domain is part of the bacterial c-di-GMP binding protein". Bioinformatics. 22 (1): 3–6. doi:10.1093/bioinformatics/bti739. PMID 16249258.
  4. ^ Mattick, JS (2002). "Type IV pili and twitching motility". Annual Review of Microbiology. 56: 289–314. doi:10.1146/annurev.micro.56.012302.160938. PMID 12142488.
  5. ^ Wolfe, AJ; Visick, KL (Jan 2008). "Get the message out: cyclic-Di-GMP regulates multiple levels of flagellum-based motility". Journal of Bacteriology. 190 (2): 463–75. doi:10.1128/JB.01418-07. PMC 2223684. PMID 17993515.
  6. ^ Paul, K; Nieto, V; Carlquist, WC; Blair, DF; Harshey, RM (Apr 9, 2010). "The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a "backstop brake" mechanism". Molecular Cell. 38 (1): 128–39. doi:10.1016/j.molcel.2010.03.001. PMC 2929022. PMID 20346719.
  7. ^ Benach, J; Swaminathan, SS; Tamayo, R; Handelman, SK; Folta-Stogniew, E; Ramos, JE; Forouhar, F; Neely, H; Seetharaman, J; Camilli, A; Hunt, JF (Dec 12, 2007). "The structural basis of cyclic diguanylate signal transduction by PilZ domains". The EMBO Journal. 26 (24): 5153–66. doi:10.1038/sj.emboj.7601918. PMC 2140105. PMID 18034161.
  8. ^ Pitzer, JE; Sultan, SZ; Hayakawa, Y; Hobbs, G; Miller, MR; Motaleb, MA (May 2011). "Analysis of the Borrelia burgdorferi cyclic-di-GMP-binding protein PlzA reveals a role in motility and virulence". Infection and Immunity. 79 (5): 1815–25. doi:10.1128/IAI.00075-11. PMC 3088147. PMID 21357718.
This article incorporates text from the public domain Pfam and InterPro: IPR009875

Category:Protein domains

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PilZ domain Provide feedback

PilZ is a c-di-GMP binding domain [3] which is found C terminal to PF07317. Proteins which contain PilZ are known to interact with the flagellar switch-complex proteins FliG and FliM. This interaction results in a reduction of torque generation and induces CCW motor bias [5]. This domain forms a beta barrel structure.

Literature references

  1. Alm RA, Bodero AJ, Free PD, Mattick JS; , J Bacteriol 1996;178:46-53.: Identification of a novel gene, pilZ, essential for type 4 fimbrial biogenesis in Pseudomonas aeruginosa. PUBMED:8550441 EPMC:8550441

  2. Amikam D, Galperin MY;, Bioinformatics. 2006;22:3-6.: PilZ domain is part of the bacterial c-di-GMP binding protein. PUBMED:16249258 EPMC:16249258

  3. Ryjenkov DA, Simm R, Romling U, Gomelsky M;, J Biol Chem. 2006;281:30310-30314.: The PilZ domain is a receptor for the second messenger c-di-GMP: the PilZ domain protein YcgR controls motility in enterobacteria. PUBMED:16920715 EPMC:16920715

  4. Benach J, Swaminathan SS, Tamayo R, Handelman SK, Folta-Stogniew E, Ramos JE, Forouhar F, Neely H, Seetharaman J, Camilli A, Hunt JF;, EMBO J. 2007;26:5153-5166.: The structural basis of cyclic diguanylate signal transduction by PilZ domains. PUBMED:18034161 EPMC:18034161

  5. Paul K, Nieto V, Carlquist WC, Blair DF, Harshey RM;, Mol Cell. 2010;38:128-139.: The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a "backstop brake" mechanism. PUBMED:20346719 EPMC:20346719


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR009875

The ubiquitous bacterial second messenger cyclic-di-GMP (c-di-GMP) is associated with the regulation of biofilm formation, the control of exopolysaccharide synthesis, flagellar- and pili-based motility, gene expression, interactions of bacteria with eukaryotic hosts and multicellular behaviour in diverse bacteria.

With the exception of bacterial cellulose synthases, the identities of c-di-GMP receptors and end targets of the proteins having one or more PilZ domains are mostly uncharacterised. However it was suggested that the PilZ domains present in the BcsA subunits of bacterial cellulose synthases function in c-di-GMP binding [PUBMED:16249258]. More recently YcgR (see INTERPRO) was found to bind c-di-GMP tightly and specifically; also isolated PilZ domains from YcgR and BcsA bound c-di-GMP indicating that the PilZ domain was sufficient for binding of c-di-GMP and significantly that site-directed mutagenesis performed on YcgR implicated the most conserved residues in the PilZ domain directly in c-di-GMP binding [PUBMED:16920715]. It was suggested that c-di-GMP binding to PilZ brings about conformational changes in the protein that stabilise the bound ligand and probability initiates the downstream signal transduction cascade. In the case of YcgR, c-di-GMP binding regulates flagellum-based motility in a c-di-GMP-dependent manner (see INTERPRO) [PUBMED:16920715]. The association of the PilZ domain with a variety of other domains, including likely components of bacterial multidrug secretion system, could provide clues to multiple functions of the c-di-GMP in bacterial pathogenesis and cell development.

Binding and mutagenesis studies of several PilZ domain proteins have confirmed this observation and demonstrated 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 [PUBMED:18034161].

Gene Ontology

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Domain organisation

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Alignments

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  Seed
(190)
Full
(13164)
Representative proteomes UniProt
(40146)
NCBI
(51951)
Meta
(331)
RP15
(3743)
RP35
(9038)
RP55
(13792)
RP75
(19910)
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  Seed
(190)
Full
(13164)
Representative proteomes UniProt
(40146)
NCBI
(51951)
Meta
(331)
RP15
(3743)
RP35
(9038)
RP55
(13792)
RP75
(19910)
Alignment:
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  Seed
(190)
Full
(13164)
Representative proteomes UniProt
(40146)
NCBI
(51951)
Meta
(331)
RP15
(3743)
RP35
(9038)
RP55
(13792)
RP75
(19910)
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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_17421 (release 10.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Galperin MY
Number in seed: 190
Number in full: 13164
Average length of the domain: 100.70 aa
Average identity of full alignment: 15 %
Average coverage of the sequence by the domain: 40.82 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.5 22.5
Trusted cut-off 22.5 22.5
Noise cut-off 22.4 22.4
Model length: 103
Family (HMM) version: 14
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Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There are 6 interactions for this family. More...

Glyco_tranf_2_3 PilZ YcgR YcgR_2 YcgR_2 EAL

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PilZ domain has been found. There are 42 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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