“Fic/DOC protein family”的意思、由来-开放百科全书

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]

Functions

First 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

1. ^¹²³⁴⁵⁶{{cite journal | vauthors = Veyron S, Peyroche G, Cherfils J | title = FIC proteins: from bacteria to humans and back again | journal = Pathogens and Disease | volume = 76 | issue = 2 | date = March 2018 | pmid = 29617857 | doi = 10.1093/femspd/fty012 }}
2. ^¹{{cite journal | vauthors = Garcia-Pino A, Zenkin N, Loris R | title = The many faces of Fic: structural and functional aspects of Fic enzymes | journal = Trends in Biochemical Sciences | volume = 39 | issue = 3 | pages = 121–9 | date = March 2014 | pmid = 24507752 | doi = 10.1016/j.tibs.2014.01.001 }}
3. ^{{cite journal | vauthors = Kawamukai M, Matsuda H, Fujii W, Nishida T, Izumoto Y, Himeno M, Utsumi R, Komano T | title = Cloning of the fic-1 gene involved in cell filamentation induced by cyclic AMP and construction of a delta fic Escherichia coli strain | journal = Journal of Bacteriology | volume = 170 | issue = 9 | pages = 3864–9 | date = September 1988 | pmid = 2842288 | pmc = 211382 }}
4. ^{{cite journal | vauthors = Stanger FV, Harms A, Dehio C, Schirmer T | title = Crystal Structure of the Escherichia coli Fic Toxin-Like Protein in Complex with Its Cognate Antitoxin | journal = PLOS One | volume = 11 | issue = 9 | pages = e0163654 | date = 2016 | pmid = 27657533 | pmc = 5033356 | doi = 10.1371/journal.pone.0163654 }}
5. ^{{cite journal | vauthors = Yarbrough ML, Li Y, Kinch LN, Grishin NV, Ball HL, Orth K | title = AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling | journal = Science | volume = 323 | issue = 5911 | pages = 269–72 | date = January 2009 | pmid = 19039103 | doi = 10.1126/science.1166382 }}
6. ^{{cite journal | vauthors = Castro-Roa D, Garcia-Pino A, De Gieter S, van Nuland NA, Loris R, Zenkin N | title = The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu | journal = Nature Chemical Biology | volume = 9 | issue = 12 | pages = 811–7 | date = December 2013 | pmid = 24141193 | pmc = 3836179 | doi = 10.1038/nchembio.1364 }}
7. ^{{cite journal | vauthors = 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 | title = Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors | journal = Science Advances | volume = 4 | issue = 3 | pages = eaap9714 | date = March 2018 | pmid = 29546243 | pmc = 5851678 | doi = 10.1126/sciadv.aap9714 }}
8. ^{{cite journal | vauthors = Komano T, Utsumi R, Kawamukai M | title = Functional analysis of the fic gene involved in regulation of cell division | journal = Research in Microbiology | volume = 142 | issue = 2-3 | pages = 269–77 | year = 1991 | pmid = 1656497 | doi = 10.1016/0923-2508(91)90040-h }}
9. ^{{cite journal | vauthors = Lehnherr H, Maguin E, Jafri S, Yarmolinsky MB | title = 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 = Journal of Molecular Biology | volume = 233 | issue = 3 | pages = 414–28 | date = October 1993 | pmid = 8411153 | doi = 10.1006/jmbi.1993.1521 }}
10. ^{{cite journal | vauthors = Preissler S, Rato C, Perera L, Saudek V, Ron D | title = FICD acts bifunctionally to AMPylate and de-AMPylate the endoplasmic reticulum chaperone BiP | journal = Nature Structural & Molecular Biology | volume = 24 | issue = 1 | pages = 23–29 | date = January 2017 | pmid = 27918543 | pmc = 5221731 | doi = 10.1038/nsmb.3337 }}