In molecular biology, the Fic/DOC protein family is a family of proteins which catalyzes the post-translational modification of proteins using phosphate-containing compound as a substrate.[1] Fic domain proteins typically use ATP as a co-factor, but in some cases GTP or UTP is used.[2] Post-translational modification performed by Fic domains is usually NMPylation (AMPylation, GMPylation or UMPylation), however they also catalyze phosphorylation and phosphocholine transfer.[2] This family contains a central conserved motif HPFX[D/E]GNGR in most members and it carries the invariant catalytic histidine.[1] Fic domain was found in bacteria, eukaryotes and archaea and can be found organized in almost hundred different multi-domain assemblies.[1]
| Fic/DOC family | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 structure of cell filamentation protein (fic) from helicobacter pylori | |||||||||
| Identifiers | |||||||||
| Symbol | Fic | ||||||||
| Pfam | PF02661 | ||||||||
| InterPro | IPR003812 | ||||||||
| |||||||||
Functions
editFirst fic gene was discovered in the late 1980s in Escherichia coli. Mutation in this gene impaired cell division under stress conditions (cyclic AMP in growth medium at high temperature), which led to annotation as fic-1 for filamentation induced by cAMP.[3][1] The product of fic-1 was later characterized as toxin from toxin-antitoxin system.[4][1] Fic domain protein from the Vibrio parahaemolyticus VopS is a toxin secreted by type III secretion system. It catalyses AMPylation of Rho GTPases in eukaryotic cells and therefore induces the collapse of the actin cytoskeleton.[5] Doc (death on curing) protein is also part of a toxin-antitoxin module Phd-Doc from prophage P1. Doc toxin uses inverted substrate and catalyses phosphorylation instead of transferring NMP moiety.[6] Doc phosphorylates elongation factor EF-Tu and locks it in an unfavorable open conformation to bind tRNAs and therefore blocks protein translation.[7] Doc provides stability for P1 lysogens of Escherichia coli. Bacteria carry the prophage as a stable low copy number plasmid. The frequency with which viable cells cured of prophage are produced is about 10(-5) per cell per generation.[8] A significant part of this remarkable stability can be attributed to a plasmid-encoded toxin-antitoxin module phd-doc causes death of cells that have lost P1.[9] Overall bacterial Fic proteins are members of toxin-antitoxin systems and other proteins involved in stress responses and infections.[1] The sole animal Fic-domain protein called HYPE or FICD is involved in proteostasis control by addition and removal of AMP from endoplasmic reticulum chaperone BIP.[10][1]
References
edit- ^ a b c d e f g Veyron S, Peyroche G, Cherfils J (March 2018). "FIC proteins: from bacteria to humans and back again". Pathogens and Disease. 76 (2). doi:10.1093/femspd/fty012. PMID 29617857.
- ^ a b Garcia-Pino A, Zenkin N, Loris R (March 2014). "The many faces of Fic: structural and functional aspects of Fic enzymes". Trends in Biochemical Sciences. 39 (3): 121–9. doi:10.1016/j.tibs.2014.01.001. PMID 24507752.
- ^ Kawamukai M, Matsuda H, Fujii W, Nishida T, Izumoto Y, Himeno M, Utsumi R, Komano T (September 1988). "Cloning of the fic-1 gene involved in cell filamentation induced by cyclic AMP and construction of a delta fic Escherichia coli strain". Journal of Bacteriology. 170 (9): 3864–9. doi:10.1128/jb.170.9.3864-3869.1988. PMC 211382. PMID 2842288.
- ^ Stanger FV, Harms A, Dehio C, Schirmer T (2016). "Crystal Structure of the Escherichia coli Fic Toxin-Like Protein in Complex with Its Cognate Antitoxin". PLOS ONE. 11 (9): e0163654. Bibcode:2016PLoSO..1163654S. doi:10.1371/journal.pone.0163654. PMC 5033356. PMID 27657533.
- ^ Yarbrough ML, Li Y, Kinch LN, Grishin NV, Ball HL, Orth K (January 2009). "AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling". Science. 323 (5911): 269–72. doi:10.1126/science.1166382. PMID 19039103. S2CID 16876108.
- ^ Castro-Roa D, Garcia-Pino A, De Gieter S, van Nuland NA, Loris R, Zenkin N (December 2013). "The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu". Nature Chemical Biology. 9 (12): 811–7. doi:10.1038/nchembio.1364. PMC 3836179. PMID 24141193.
- ^ Talavera A, Hendrix J, Versées W, Jurėnas D, Van Nerom K, Vandenberk N, Singh RK, Konijnenberg A, De Gieter S, Castro-Roa D, Barth A, De Greve H, Sobott F, Hofkens J, Zenkin N, Loris R, Garcia-Pino A (March 2018). "Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors". Science Advances. 4 (3): eaap9714. Bibcode:2018SciA....4.9714T. doi:10.1126/sciadv.aap9714. PMC 5851678. PMID 29546243.
- ^ Komano T, Utsumi R, Kawamukai M (1991). "Functional analysis of the fic gene involved in regulation of cell division". Research in Microbiology. 142 (2–3): 269–77. doi:10.1016/0923-2508(91)90040-h. PMID 1656497.
- ^ Lehnherr H, Maguin E, Jafri S, Yarmolinsky MB (October 1993). "Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained". Journal of Molecular Biology. 233 (3): 414–28. doi:10.1006/jmbi.1993.1521. PMID 8411153.
- ^ Preissler S, Rato C, Perera L, Saudek V, Ron D (January 2017). "FICD acts bifunctionally to AMPylate and de-AMPylate the endoplasmic reticulum chaperone BiP". Nature Structural & Molecular Biology. 24 (1): 23–29. doi:10.1038/nsmb.3337. PMC 5221731. PMID 27918543.