Fic/DOC protein family

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Fic/DOC family
PDB 2f6s EBI.jpg
structure of cell filamentation protein (fic) from helicobacter pylori
Identifiers
SymbolFic
Pfam PF02661
InterPro IPR003812
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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]

Related Research Articles

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<span class="mw-page-title-main">SOS response</span> Biological process

The SOS response is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis is induced. The system involves the RecA protein. The RecA protein, stimulated by single-stranded DNA, is involved in the inactivation of the repressor (LexA) of SOS response genes thereby inducing the response. It is an error-prone repair system that contributes significantly to DNA changes observed in a wide range of species.

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<span class="mw-page-title-main">Sib RNA</span>

Sib RNA refers to a group of related non-coding RNA. They were originally named QUAD RNA after they were discovered as four repeat elements in Escherichia coli intergenic regions. The family was later renamed Sib when it was discovered that the number of repeats is variable in other species and in other E. coli strains.

<span class="mw-page-title-main">Hok/sok system</span>

The hok/sok system is a postsegregational killing mechanism employed by the R1 plasmid in Escherichia coli. It was the first type I toxin-antitoxin pair to be identified through characterisation of a plasmid-stabilising locus. It is a type I system because the toxin is neutralised by a complementary RNA, rather than a partnered protein.

<span class="mw-page-title-main">Adenylylation</span> Biological process

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<span class="mw-page-title-main">Toxin-antitoxin system</span> Biological process

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<span class="mw-page-title-main">LdrD-RdlD toxin-antitoxin system</span>

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<span class="mw-page-title-main">SymE-SymR toxin-antitoxin system</span>

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<span class="mw-page-title-main">FlmA-FlmB toxin-antitoxin system</span>

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par stability determinant

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vapBC

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FIC domain protein adenylyltransferase (FICD) is an enzyme in metazoans possessing adenylylation and deadenylylation activity (also known as (de)AMPylation), and is a member of the Fic (filamentation induced by cAMP) domain family of proteins. AMPylation is a reversible post-translational modification that FICD performs on target cellular protein substrates. FICD is the only known Fic domain encoded by the metazoan genome, and is located on chromosome 12 in humans. Catalytic activity is reliant on the enzyme's Fic domain, which catalyzes the addition of an AMP (adenylyl group) moiety to the substrate. FICD has been linked to many cellular pathways, most notably the ATF6 and PERK branches of the UPR (unfolded protein response) pathway regulating ER homeostasis. FICD is present at very low basal levels in most cell types in humans, and its expression is highly regulated. Examples of FICD include HYPE (Huntingtin Yeast Interacting Partner E) in humans, Fic-1 in C. elegans, and dfic in D. melanogaster.

References

  1. 1 2 3 4 5 6 7 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.
  2. 1 2 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
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