Escherichia coli K-12 substr. MG1655 Polypeptide: dipeptide ABC transporter - periplasmic binding protein

Gene: dppA Accession Numbers: EG10248 (EcoCyc), b3544, ECK3531

Synonyms: alu, dpp, fpp

Regulation Summary Diagram: ?

Regulation summary diagram for dppA

Component of: dipeptide ABC transporter (extended summary available)

DppA is the periplasmic binding component of the dipeptide ABC transporter.

Gene Citations: [Abouhamad94]

Locations: periplasmic space, inner membrane

Map Position: [3,704,121 <- 3,705,728] (79.84 centisomes, 287°)
Length: 1608 bp / 535 aa

Molecular Weight of Polypeptide: 60.294 kD (from nucleotide sequence), 50.0 kD (experimental) [Olson91 ]

Unification Links: ASAP:ABE-0011576 , CGSC:35111 , DIP:DIP-9467N , EchoBASE:EB0244 , EcoGene:EG10248 , EcoliWiki:b3544 , Mint:MINT-1240350 , ModBase:P23847 , OU-Microarray:b3544 , PortEco:dppA , PR:PRO_000022473 , Pride:P23847 , Protein Model Portal:P23847 , RefSeq:NP_418001 , RegulonDB:EG10248 , SMR:P23847 , String:511145.b3544 , UniProt:P23847

Relationship Links: InterPro:IN-FAMILY:IPR000914 , InterPro:IN-FAMILY:IPR023765 , PDB:Structure:1DPE , PDB:Structure:1DPP , Pfam:IN-FAMILY:PF00496 , Prosite:IN-FAMILY:PS01040

In Paralogous Gene Group: 25 (11 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for dppA

GO Terms:

Biological Process: GO:0042938 - dipeptide transport Inferred from experiment [Olson91]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11]
GO:0006935 - chemotaxis Inferred by computational analysis [UniProtGOA11]
GO:0015031 - protein transport Inferred by computational analysis [UniProtGOA11]
GO:0015833 - peptide transport Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0042277 - peptide binding Inferred from experiment [Smith99]
GO:0042936 - dipeptide transporter activity Inferred from experiment [Olson91]
GO:0015421 - oligopeptide-transporting ATPase activity Inferred by computational analysis [Abouhamad94]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred from experiment Inferred by computational analysis [DiazMejia09, Han13, Molloy00, LopezCampistrou05, Olson91]
GO:0042597 - periplasmic space Inferred by computational analysis [UniProtGOA11a, UniProtGOA11]
GO:0043190 - ATP-binding cassette (ABC) transporter complex Inferred by computational analysis [Abouhamad94]

MultiFun Terms: metabolism carbon utilization amino acids
transport Channel-type Transporters Pyrophosphate Bond (ATP; GTP; P2) Hydrolysis-driven Active Transporters The ATP-binding Cassette (ABC) Superfamily + ABC-type Uptake Permeases ABC superfamily, periplasmic binding component

Essentiality data for dppA 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]
Yes [Feist07, Comment 4]

Subunit of: dipeptide ABC transporter

Synonyms: DppABCDF

Subunit composition of dipeptide ABC transporter = [DppD][DppF][DppB][DppC][DppA]
         dipeptide ABC transporter - putative ATP binding subunit = DppD (summary available)
         dipeptide ABC transporter - putative ABC binding subunit = DppF (summary available)
         dipeptide ABC transporter - putative membrane subunit = DppB (summary available)
         dipeptide ABC transporter - putative membrane subunit = DppC (summary available)
         dipeptide ABC transporter - periplasmic binding protein = DppA (summary available)

The DppABCDF dipeptide transport system is a member of the ATP-Binding Cassette (ABC) Superfamily of transporters [Wu95]. Based on sequence similarity, DppA is the substrate-binding component, while DppB and DppC are the membrane components, and DppD and DppF are the ATP-binding components of the ABC transporter. DppABCDF is similar in sequence and subunit composition to the oligopeptide uptake system OppABCDF, suggesting similar subunit functions.

DppA's unbound structure has been resolved by x-ray crystallography to resolutions of 3.2 Å [Dunten93] and 2.0 Å, and shows two domains connected by two 'hinge' segments [Nickitenko95]. The structure of DppA has also been determined with bound glycyl-L-leucine has been determined to a resolution of 3.2 Å [Dunten95]. The structure reveals that the binding site recognizes the peptide backbone allowing for accommodation of various side chains [Dunten95]. There is also a requirement for an unsubstituted α-amino group for transport of a peptide [Gilvarg65].

Loss of DppA or DppBCDF resulted in pro mutants being unable to utilize Pro-Gly as a proline source [Olson91]. Pro-Gly transport was inhibited by His-Glu, suggesting His-Glu is an additional substrate for DppABCDF [Olson91]. Mutations in dpp displayed resistance to the toxic dipeptide Lys-aminoxyAla, the loss of ability to utilize Leu-Trp as a source of its required amino acids [Payne84], resistance to Gly-Val, Leu-Val, and Val-Leu, and reduced uptake of Gly-Gly [De73]. Substrate specificity of DppA was studied in a filter binding assay in which column fractions were monitored for binding activity towards radioactively labeled dipeptides and tripeptides. DppA was observed to mediate the ATP driven uptake of dipeptides and, to a lesser extent, tripeptides from the periplasm [Smith99]. When an outer membrane heme receptor is expressed in E. coli, the dipeptide ABC transporter is also capable of transporting heme and the heme precursor, δ aminolevulinic acid, from the periplasm into the cytoplasm [Letoffe06]. Binding of heme to purified DppA has been demonstrated [Letoffe06].

DppA accumulates to high levels when grown in minimal media, but levels of DppA are reduced when the medium is supplemented with casamino acids [Olson91]. DppA levels were decreased after 4 hours exposure to zinc stress [Easton06] and in response to glucose limitation [Wick01]. When grown in rich medium, gcvB deletion mutants had high constitutive expression of dppA compared to the parent strain [Urbanowski00]. dppA expression is also repressed by PhoB during phosphate limitation [Smith92].

Citations: [Rinas04, Payne79a, Marshall03, Payne01]

Enzymatic reaction of: Transport of a dipeptide (dipeptide ABC transporter)

Transport reaction diagram for Transport of a dipeptide

Alternative Products for a dipeptide: 5-aminolevulinate [Letoffe06 , Verkamp93 ] , heme [Letoffe06 ] , tyr-FMDP [Marshall03 ] , nva-FMDB [Marshall03 ] , val-FMDP [Marshall03 ] , phe-FMDP [Marshall03 ] , nva-FMDP [Marshall03 ] , met-FMDP [Marshall03 ] , lys-FMDP [Marshall03 ] , leu-FMDP [Marshall03 ] , L-alanyl-L-α-thiophenylglycine [Perry84 ] , lys-aminoxyAla [Smith99 ] , glycylsarcosine [Payne01 ]

Sequence Features

Protein sequence of dipeptide ABC transporter - periplasmic binding protein with features indicated

Feature Class Location Common Name Citations Comment
Signal-Sequence 1 -> 28 DppA signal sequence
[Abouhamad91, Wilkins98, Link97, Olson91]
Chain 29 -> 535  
UniProt: Periplasmic dipeptide transport protein;
Disulfide-Bond-Site 34, 262  
[Dunten95a, UniProt15]
Disulfide-Bond-Site 450, 463  
[Dunten95a, UniProt15]

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


10/20/97 Gene b3544 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10248; confirmed by SwissProt match.


Abouhamad91: Abouhamad WN, Manson M, Gibson MM, Higgins CF (1991). "Peptide transport and chemotaxis in Escherichia coli and Salmonella typhimurium: characterization of the dipeptide permease (Dpp) and the dipeptide-binding protein." Mol Microbiol 5(5);1035-47. PMID: 1956284

Abouhamad94: Abouhamad WN, Manson MD (1994). "The dipeptide permease of Escherichia coli closely resembles other bacterial transport systems and shows growth-phase-dependent expression." Mol Microbiol 1994;14(5);1077-92. PMID: 7536291

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

De73: De Felice M, Guardiola J, Lamberti A, Iaccarino M (1973). "Escherichia coli K-12 mutants altered in the transport systems for oligo- and dipeptides." J Bacteriol 116(2);751-6. PMID: 4126826

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

Dunten93: Dunten PW, Harris JH, Feiz V, Mowbray SL (1993). "Crystallization and preliminary X-ray analysis of the periplasmic dipeptide binding protein from Escherichia coli." J Mol Biol 231(1);145-7. PMID: 8496961

Dunten95: Dunten P, Mowbray SL (1995). "Crystal structure of the dipeptide binding protein from Escherichia coli involved in active transport and chemotaxis." Protein Sci 4(11);2327-34. PMID: 8563629

Dunten95a: Dunten P. (1995). Data submission to UniProtKB on 1995-06.

Easton06: Easton JA, Thompson P, Crowder MW (2006). "Time-dependent translational response of E. coli to excess Zn(II)." J Biomol Tech 17(5);303-7. PMID: 17122063

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

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

Gilvarg65: Gilvarg C, Katchalski E (1965). "Peptide utilization in Escherichia coli." J Biol Chem 240;3093-8. PMID: 14342337

Han13: Han MJ, Kim JY, Kim JA (2013). "Comparison of the large-scale periplasmic proteomes of the Escherichia coli K-12 and B strains." J Biosci Bioeng. PMID: 24140104

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

Letoffe06: Letoffe S, Delepelaire P, Wandersman C (2006). "The housekeeping dipeptide permease is the Escherichia coli heme transporter and functions with two optional peptide binding proteins." Proc Natl Acad Sci U S A 103(34);12891-6. PMID: 16905647

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

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Marshall03: Marshall NJ, Andruszkiewicz R, Gupta S, Milewski S, Payne JW (2003). "Structure-activity relationships for a series of peptidomimetic antimicrobial prodrugs containing glutamine analogues." J Antimicrob Chemother 51(4);821-31. PMID: 12654735

Molloy00: Molloy MP, Herbert BR, Slade MB, Rabilloud T, Nouwens AS, Williams KL, Gooley AA (2000). "Proteomic analysis of the Escherichia coli outer membrane." Eur J Biochem 267(10);2871-81. PMID: 10806384

Nickitenko95: Nickitenko AV, Trakhanov S, Quiocho FA (1995). "2 A resolution structure of DppA, a periplasmic dipeptide transport/chemosensory receptor." Biochemistry 34(51);16585-95. PMID: 8527431

Olson91: Olson ER, Dunyak DS, Jurss LM, Poorman RA (1991). "Identification and characterization of dppA, an Escherichia coli gene encoding a periplasmic dipeptide transport protein." J Bacteriol 173(1);234-44. PMID: 1702779

Payne01: Payne JW, Payne GM, Gupta S, Marshall NJ, Grail BM (2001). "Conformational limitations of glycylsarcosine as a prototypic substrate for peptide transporters." Biochim Biophys Acta 1514(1);65-75. PMID: 11513805

Payne79a: Payne JW, Bell G (1979). "Direct determination of the properties of peptide transport systems in Escherichia coli, using a fluorescent-labeling procedure." J Bacteriol 137(1);447-55. PMID: 368023

Payne84: Payne JW, Morley JS, Armitage P, Payne GM (1984). "Transport and hydrolysis of antibacterial peptide analogues in Escherichia coli: backbone-modified aminoxy peptides." J Gen Microbiol 1984;130 ( Pt 9);2253-65. PMID: 6389761

Perry84: Perry D, Gilvarg C (1984). "Spectrophotometric determination of affinities of peptides for their transport systems in Escherichia coli." J Bacteriol 160(3);943-8. PMID: 6389518

Rinas04: Rinas U, Hoffmann F (2004). "Selective leakage of host-cell proteins during high-cell-density cultivation of recombinant and non-recombinant Escherichia coli." Biotechnol Prog 20(3);679-87. PMID: 15176868

Smith92: Smith MW, Payne JW (1992). "Expression of periplasmic binding proteins for peptide transport is subject to negative regulation by phosphate limitation in Escherichia coli." FEMS Microbiol Lett 79(1-3);183-90. PMID: 1478454

Smith99: Smith MW, Tyreman DR, Payne GM, Marshall NJ, Payne JW (1999). "Substrate specificity of the periplasmic dipeptide-binding protein from Escherichia coli: experimental basis for the design of peptide prodrugs." Microbiology 1999;145 ( Pt 10);2891-901. PMID: 10537211

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

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 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."

Urbanowski00: Urbanowski ML, Stauffer LT, Stauffer GV (2000). "The gcvB gene encodes a small untranslated RNA involved in expression of the dipeptide and oligopeptide transport systems in Escherichia coli." Mol Microbiol 37(4);856-68. PMID: 10972807

Verkamp93: Verkamp E, Backman VM, Bjornsson JM, Soll D, Eggertsson G (1993). "The periplasmic dipeptide permease system transports 5-aminolevulinic acid in Escherichia coli." J Bacteriol 175(5);1452-6. PMID: 8444807

Wick01: Wick LM, Quadroni M, Egli T (2001). "Short- and long-term changes in proteome composition and kinetic properties in a culture of Escherichia coli during transition from glucose-excess to glucose-limited growth conditions in continuous culture and vice versa." Environ Microbiol 3(9);588-99. PMID: 11683869

Wilkins98: Wilkins MR, Gasteiger E, Tonella L, Ou K, Tyler M, Sanchez JC, Gooley AA, Walsh BJ, Bairoch A, Appel RD, Williams KL, Hochstrasser DF (1998). "Protein identification with N and C-terminal sequence tags in proteome projects." J Mol Biol 278(3);599-608. PMID: 9600841

Wu95: Wu LF, Mandrand-Berthelot MA (1995). "A family of homologous substrate-binding proteins with a broad range of substrate specificity and dissimilar biological functions." Biochimie 1995;77(9);744-50. PMID: 8789466

Other References Related to Gene Regulation

Beisel11: Beisel CL, Storz G (2011). "The base-pairing RNA spot 42 participates in a multioutput feedforward loop to help enact catabolite repression in Escherichia coli." Mol Cell 41(3);286-97. PMID: 21292161

Constantinidou06: Constantinidou C, Hobman JL, Griffiths L, Patel MD, Penn CW, Cole JA, Overton TW (2006). "A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth." J Biol Chem 281(8);4802-15. PMID: 16377617

Maciag11: Maciag A, Peano C, Pietrelli A, Egli T, De Bellis G, Landini P (2011). "In vitro transcription profiling of the {sigma}S subunit of bacterial RNA polymerase: re-definition of the {sigma}S regulon and identification of {sigma}S-specific promoter sequence elements." Nucleic Acids Res 39(13);5338-55. PMID: 21398637

Pulvermacher08: Pulvermacher SC, Stauffer LT, Stauffer GV (2008). "The role of the small regulatory RNA GcvB in GcvB/mRNA posttranscriptional regulation of oppA and dppA in Escherichia coli." FEMS Microbiol Lett 281(1);42-50. PMID: 18312576

Urban07: Urban JH, Vogel J (2007). "Translational control and target recognition by Escherichia coli small RNAs in vivo." Nucleic Acids Res 35(3);1018-37. PMID: 17264113

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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