Escherichia coli K-12 substr. MG1655 Polypeptide: energy-dependent translational throttle protein

Gene: ettA Accession Numbers: EG12343 (EcoCyc), b4391, ECK4383

Synonyms: yjjK

Regulation Summary Diagram: ?

Regulation summary diagram for ettA

EttA is a translation factor that gates ribosome entry into the translation elongation cycle through a nucleotide-dependent interaction that is sensitive to the ATP/ADP ratio. Higher amounts of ATP relieve ADP-dependent inhibition of protein synthesis by EttA, suggesting that the elevated ADP/ATP ratio found in energy-depleted cells leads to stabilization of 70S translation initiation complexes in a hibernating conformation [Boel14]. Mechanistically, EttA modulates the movements of the ribosome and tRNAs that are required for polypeptide elongation. A model for regulation of translation by EttA has been proposed [Chen14a].

EttA is a member of the ATP-binding cassette F (ABC-F) protein family with two ABC domains, each containing an insertion in the loop after the first of the three α helices in the ABCα subdomain, and separated by an 81 residue linker domain [Boel14]. A cryo-EM structure of EttA bound to the ribosome showed that the linker domain is a P-site tRNA-interaction domain [Chen14a]. A crystal structure of EttA has been solved at 2.4 Å resolution, showing a domain-swapped dimer. Soluble EttA exists in a slowly reversible monomer-dimer equilibrium that favors the monomeric form at concentrations found in vivo [Boel14].

The ATPase activity of wild type EttA is stimulated by the presence of ribosomes. The EttA-EQ2 mutant, which is expected to prevent ATP hydrolysis and trap EttA in its ATP-bound conformation, has a dominant negative effect on growth by inhibiting protein synthesis after formation of the first peptide bond [Boel14]. ATP-bound EttA-EQ2 binds to the ribosomal E site and kinetically traps the ribosomal PRE complex in the MS-I state [Chen14a]. An ettA deletion strain shows decreased survival of long-term stationary phase [Boel14].

EttA: energy-dependent translational throttle A [Boel14]

Comment: [Fredrick14]

Citations: [Linton98, ParadisBleau14]

Locations: inner membrane, cytosol

Map Position: [4,626,878 <- 4,628,545] (99.72 centisomes, 359°)
Length: 1668 bp / 555 aa

Molecular Weight of Polypeptide: 62.443 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0014400 , DIP:DIP-48138N , EchoBASE:EB2247 , EcoGene:EG12343 , EcoliWiki:b4391 , Mint:MINT-1222078 , OU-Microarray:b4391 , PortEco:yjjK , Pride:P0A9W3 , Protein Model Portal:P0A9W3 , RefSeq:NP_418808 , RegulonDB:EG12343 , SMR:P0A9W3 , String:511145.b4391 , UniProt:P0A9W3

Relationship Links: InterPro:IN-FAMILY:IPR003439 , InterPro:IN-FAMILY:IPR003593 , InterPro:IN-FAMILY:IPR017871 , InterPro:IN-FAMILY:IPR022374 , InterPro:IN-FAMILY:IPR027417 , PDB:Structure:3J5S , PDB:Structure:4FIN , Pfam:IN-FAMILY:PF00005 , Prosite:IN-FAMILY:PS00211 , Prosite:IN-FAMILY:PS50893 , Smart:IN-FAMILY:SM00382

In Paralogous Gene Group: 23 (75 members)

GO Terms:

Biological Process: GO:0045900 - negative regulation of translational elongation Inferred from experiment [Boel14]
GO:0006412 - translation Inferred by computational analysis [UniProtGOA11]
GO:0006417 - regulation of translation Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0016887 - ATPase activity Inferred from experiment Inferred by computational analysis [GOA01, Boel14]
GO:0043022 - ribosome binding Inferred from experiment [Chen14a]
GO:0000049 - tRNA binding Inferred by computational analysis [UniProtGOA11]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0003723 - RNA binding Inferred by computational analysis [UniProtGOA11]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0019843 - rRNA binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11a, UniProtGOA11]
GO:0005829 - cytosol
GO:0005886 - plasma membrane Inferred by computational analysis [DiazMejia09]

MultiFun Terms: information transfer protein related translation

Essentiality data for ettA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Last-Curated ? 15-Jan-2014 by Keseler I , SRI International

Sequence Features

Protein sequence of energy-dependent translational throttle protein with features indicated

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Link97, UniProt11a]
UniProt: Removed.
Chain 2 -> 555
UniProt: Uncharacterized ABC transporter ATP- binding protein yjjK;
Conserved-Region 6 -> 259
UniProt: ABC transporter 1;
Nucleotide-Phosphate-Binding-Region 39 -> 46
UniProt: ATP 1; Non-Experimental Qualifier: potential;
Protein-Segment 95 -> 139
UniProt: Arm; Sequence Annotation Type: region of interest.
Mutagenesis-Variant 188
[Chen14a, Boel14, UniProt14]
UniProt: Arrests growth, inhibits tripeptide but not dipeptide formation, stably binds 70S ribosomes, probably locked in an ATP-bound form as it should not have ATPase activity; when associated with Q-470.
Protein-Segment 242 -> 322
UniProt: PtIM; Sequence Annotation Type: region of interest.
Conserved-Region 324 -> 550
UniProt: ABC transporter 2;
Nucleotide-Phosphate-Binding-Region 356 -> 363
UniProt: ATP 2; Non-Experimental Qualifier: potential;
Mutagenesis-Variant 470
[Chen14a, Boel14, UniProt14]
UniProt: Arrests growth, inhibits tripeptide but not dipeptide formation, stably binds 70S ribosomes, probably locked in an ATP-bound form as it should not have ATPase activity; when associated with Q-188.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b4391 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12343.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Boel14: Boel G, Smith PC, Ning W, Englander MT, Chen B, Hashem Y, Testa AJ, Fischer JJ, Wieden HJ, Frank J, Gonzalez RL, Hunt JF (2014). "The ABC-F protein EttA gates ribosome entry into the translation elongation cycle." Nat Struct Mol Biol 21(2);143-51. PMID: 24389466

Chen14a: Chen B, Boel G, Hashem Y, Ning W, Fei J, Wang C, Gonzalez RL, Hunt JF, Frank J (2014). "EttA regulates translation by binding the ribosomal E site and restricting ribosome-tRNA dynamics." Nat Struct Mol Biol 21(2);152-9. PMID: 24389465

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Fredrick14: Fredrick K, Ibba M (2014). "The ABCs of the ribosome." Nat Struct Mol Biol 21(2);115-6. PMID: 24500425

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Link97: Link AJ, Robison K, Church GM (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18(8);1259-313. PMID: 9298646

Linton98: Linton KJ, Higgins CF (1998). "The Escherichia coli ATP-binding cassette (ABC) proteins." Mol Microbiol 1998;28(1);5-13. PMID: 9593292

ParadisBleau14: Paradis-Bleau C, Kritikos G, Orlova K, Typas A, Bernhardt TG (2014). "A genome-wide screen for bacterial envelope biogenesis mutants identifies a novel factor involved in cell wall precursor metabolism." PLoS Genet 10(1);e1004056. PMID: 24391520

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt14: UniProt Consortium (2014). "UniProt version 2014-08 released on 2014-08-01 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Tue Oct 6, 2015, biocyc13.