MSBA_ECOLI
ID MSBA_ECOLI Reviewed; 582 AA.
AC P60752; P27299;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=ATP-dependent lipid A-core flippase {ECO:0000255|HAMAP-Rule:MF_01703, ECO:0000305};
DE EC=7.5.2.6 {ECO:0000255|HAMAP-Rule:MF_01703, ECO:0000269|PubMed:15304478, ECO:0000269|PubMed:20412049, ECO:0000269|PubMed:28869968};
DE AltName: Full=Lipid A export ATP-binding/permease protein MsbA {ECO:0000255|HAMAP-Rule:MF_01703, ECO:0000305};
DE AltName: Full=Lipid flippase {ECO:0000303|PubMed:12119303};
GN Name=msbA {ECO:0000255|HAMAP-Rule:MF_01703, ECO:0000303|PubMed:8094880};
GN OrderedLocusNames=b0914, JW0897;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=8094880; DOI=10.1111/j.1365-2958.1993.tb01098.x;
RA Karow M.L., Georgopoulos C.;
RT "The essential Escherichia coli msbA gene, a multicopy suppressor of null
RT mutations in the htrB gene, is related to the universally conserved family
RT of ATP-dependent translocators.";
RL Mol. Microbiol. 7:69-79(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-511 AND ASP-512.
RX PubMed=8809774; DOI=10.1111/j.1365-2958.1996.tb02642.x;
RA Polissi A., Georgopoulos C.;
RT "Mutational analysis and properties of the msbA gene of Escherichia coli,
RT coding for an essential ABC family transporter.";
RL Mol. Microbiol. 20:1221-1233(1996).
RN [6]
RP FUNCTION IN TRANSPORT, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9575204; DOI=10.1074/jbc.273.20.12466;
RA Zhou Z., White K.A., Polissi A., Georgopoulos C., Raetz C.R.H.;
RT "Function of Escherichia coli MsbA, an essential ABC family transporter, in
RT lipid A and phospholipid biosynthesis.";
RL J. Biol. Chem. 273:12466-12475(1998).
RN [7]
RP MUTAGENESIS OF ALA-270.
RC STRAIN=LBC273;
RX PubMed=11278265; DOI=10.1074/jbc.c100091200;
RA Doerrler W.T., Reedy M.C., Raetz C.R.H.;
RT "An Escherichia coli mutant defective in lipid export.";
RL J. Biol. Chem. 276:11461-11464(2001).
RN [8]
RP FUNCTION, ATPASE ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ALA-270.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=12119303; DOI=10.1074/jbc.m205857200;
RA Doerrler W.T., Raetz C.R.H.;
RT "ATPase activity of the MsbA lipid flippase of Escherichia coli.";
RL J. Biol. Chem. 277:36697-36705(2002).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15304478; DOI=10.1074/jbc.m408106200;
RA Doerrler W.T., Gibbons H.S., Raetz C.R.;
RT "MsbA-dependent translocation of lipids across the inner membrane of
RT Escherichia coli.";
RL J. Biol. Chem. 279:45102-45109(2004).
RN [10]
RP SUBCELLULAR LOCATION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15919996; DOI=10.1126/science.1109730;
RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.;
RT "Global topology analysis of the Escherichia coli inner membrane
RT proteome.";
RL Science 308:1321-1323(2005).
RN [11]
RP RETRACTED PAPER.
RX PubMed=11546864; DOI=10.1126/science.293.5536.1793;
RA Chang G., Roth C.B.;
RT "Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP
RT binding cassette (ABC) transporters.";
RL Science 293:1793-1800(2001).
RN [12]
RP RETRACTION NOTICE OF PUBMED:11546864.
RX PubMed=17185584; DOI=10.1126/science.314.5807.1875b;
RA Chang G., Roth C.B., Reyes C.L., Pornillos O., Chen Y.J., Chen A.P.;
RL Science 314:1875-1875(2006).
RN [13]
RP SUBUNIT, AND DOMAIN.
RX PubMed=17927448; DOI=10.1371/journal.pbio.0050271;
RA Borbat P.P., Surendhran K., Bortolus M., Zou P., Freed J.H.,
RA Mchaourab H.S.;
RT "Conformational motion of the ABC transporter MsbA induced by ATP
RT hydrolysis.";
RL PLoS Biol. 5:e271-e271(2007).
RN [14]
RP FUNCTION, ATPASE ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND DOMAIN.
RX PubMed=18344567; DOI=10.1074/jbc.m708274200;
RA Eckford P.D., Sharom F.J.;
RT "Functional characterization of Escherichia coli MsbA: interaction with
RT nucleotides and substrates.";
RL J. Biol. Chem. 283:12840-12850(2008).
RN [15]
RP FUNCTION, ATPASE ACTIVITY, SUBUNIT, DOMAIN, AND MUTAGENESIS OF CYS-88 AND
RP CYS-315.
RX PubMed=19132955; DOI=10.1042/bj20081364;
RA Siarheyeva A., Sharom F.J.;
RT "The ABC transporter MsbA interacts with lipid A and amphipathic drugs at
RT different sites.";
RL Biochem. J. 419:317-328(2009).
RN [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20412049; DOI=10.1042/bj20100144;
RA Eckford P.D., Sharom F.J.;
RT "The reconstituted Escherichia coli MsbA protein displays lipid flippase
RT activity.";
RL Biochem. J. 429:195-203(2010).
RN [17]
RP DOMAIN, AND MUTAGENESIS OF GLU-208.
RX PubMed=20715055; DOI=10.1002/prot.22813;
RA Doshi R., Woebking B., van Veen H.W.;
RT "Dissection of the conformational cycle of the multidrug/lipid A ABC
RT exporter MsbA.";
RL Proteins 78:2867-2872(2010).
RN [18]
RP ATPASE ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF GLU-506
RP AND HIS-537.
RX PubMed=21462989; DOI=10.1021/bi101666p;
RA Schultz K.M., Merten J.A., Klug C.S.;
RT "Characterization of the E506Q and H537A dysfunctional mutants in the E.
RT coli ABC transporter MsbA.";
RL Biochemistry 50:3599-3608(2011).
RN [19]
RP DOMAIN, AND MUTAGENESIS OF GLU-208 AND LYS-212.
RX PubMed=23306205; DOI=10.1074/jbc.m112.430074;
RA Doshi R., Ali A., Shi W., Freeman E.V., Fagg L.A., van Veen H.W.;
RT "Molecular disruption of the power stroke in the ATP-binding cassette
RT transport protein MsbA.";
RL J. Biol. Chem. 288:6801-6813(2013).
RN [20]
RP DOMAIN.
RX PubMed=23766512; DOI=10.1074/jbc.m113.485714;
RA Doshi R., van Veen H.W.;
RT "Substrate binding stabilizes a pre-translocation intermediate in the ATP-
RT binding cassette transport protein MsbA.";
RL J. Biol. Chem. 288:21638-21647(2013).
RN [21]
RP PROTON-COUPLED EFFLUX.
RX PubMed=27499013; DOI=10.1038/ncomms12387;
RA Singh H., Velamakanni S., Deery M.J., Howard J., Wei S.L., van Veen H.W.;
RT "ATP-dependent substrate transport by the ABC transporter MsbA is proton-
RT coupled.";
RL Nat. Commun. 7:12387-12387(2016).
RN [22]
RP IDENTIFICATION AS A DRUG TARGET.
RX PubMed=30104274; DOI=10.1128/aac.01142-18;
RA Alexander M.K., Miu A., Oh A., Reichelt M., Ho H., Chalouni C., Labadie S.,
RA Wang L., Liang J., Nickerson N.N., Hu H., Yu L., Du M., Yan D., Park S.,
RA Kim J., Xu M., Sellers B.D., Purkey H.E., Skelton N.J., Koehler M.F.T.,
RA Payandeh J., Verma V., Xu Y., Koth C.M., Nishiyama M.;
RT "Disrupting Gram-negative bacterial outer membrane biosynthesis through
RT inhibition of the lipopolysaccharide transporter MsbA.";
RL Antimicrob. Agents Chemother. 62:0-0(2018).
RN [23] {ECO:0007744|PDB:3B5W}
RP X-RAY CRYSTALLOGRAPHY (5.30 ANGSTROMS), SUBUNIT, AND DOMAIN.
RX PubMed=18024585; DOI=10.1073/pnas.0709388104;
RA Ward A., Reyes C.L., Yu J., Roth C.B., Chang G.;
RT "Flexibility in the ABC transporter MsbA: Alternating access with a
RT twist.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:19005-19010(2007).
RN [24]
RP STRUCTURE BY ELECTRON MICROSCOPY, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, SUBUNIT, AND DOMAIN.
RX PubMed=28869968; DOI=10.1038/nature23649;
RA Mi W., Li Y., Yoon S.H., Ernst R.K., Walz T., Liao M.;
RT "Structural basis of MsbA-mediated lipopolysaccharide transport.";
RL Nature 549:233-237(2017).
RN [25] {ECO:0007744|PDB:6UZ2, ECO:0007744|PDB:6UZL}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS).
RX PubMed=32125274; DOI=10.7554/elife.53530;
RA Angiulli G., Dhupar H.S., Suzuki H., Wason I.S., Duong Van Hoa F., Walz T.;
RT "New approach for membrane protein reconstitution into peptidiscs and basis
RT for their adaptability to different proteins.";
RL Elife 9:e53530-e53530(2020).
CC -!- FUNCTION: Involved in lipopolysaccharide (LPS) biosynthesis.
CC Translocates lipid A-core from the inner to the outer leaflet of the
CC inner membrane (PubMed:8809774, PubMed:9575204, PubMed:12119303,
CC PubMed:15304478, PubMed:28869968). Transmembrane domains (TMD) form a
CC pore in the inner membrane and the ATP-binding domain (NBD) is
CC responsible for energy generation (PubMed:12119303). Shows ATPase
CC activity (PubMed:12119303, PubMed:18024585, PubMed:18344567,
CC PubMed:19132955, PubMed:20412049, PubMed:21462989). May transport
CC glycerophospholipids (PubMed:9575204). In proteoliposomes, mediates the
CC ATP-dependent flipping of a variety of phospholipid and glycolipid
CC derivatives (PubMed:20412049). May also function as a multidrug
CC transporter (PubMed:19132955). {ECO:0000269|PubMed:12119303,
CC ECO:0000269|PubMed:15304478, ECO:0000269|PubMed:18024585,
CC ECO:0000269|PubMed:18344567, ECO:0000269|PubMed:19132955,
CC ECO:0000269|PubMed:20412049, ECO:0000269|PubMed:21462989,
CC ECO:0000269|PubMed:28869968, ECO:0000269|PubMed:8809774,
CC ECO:0000269|PubMed:9575204}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + lipid A-core oligosaccharideSide 1 = ADP +
CC phosphate + lipid A-core oligosaccharideSide 2.; EC=7.5.2.6;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01703,
CC ECO:0000269|PubMed:15304478, ECO:0000269|PubMed:20412049,
CC ECO:0000269|PubMed:28869968};
CC -!- ACTIVITY REGULATION: ATPase activity is stimulated by lipid A,
CC hexaacylated lipid A or Kdo(2)-lipid A (PubMed:12119303,
CC PubMed:18344567). Inhibited by the phosphate analog vanadate
CC (PubMed:12119303, PubMed:18344567, PubMed:28869968). ATPase activity is
CC also modulated by the lipid-based drugs D-20133 and D-21266, along with
CC LY335979 and leupeptin (PubMed:18344567). {ECO:0000269|PubMed:12119303,
CC ECO:0000269|PubMed:18344567, ECO:0000269|PubMed:28869968}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=878 uM for ATP {ECO:0000269|PubMed:12119303};
CC KM=117 uM for ATP {ECO:0000269|PubMed:21462989};
CC Vmax=37 nmol/min/mg enzyme {ECO:0000269|PubMed:12119303};
CC Vmax=68 nmol/min/mg enzyme {ECO:0000269|PubMed:21462989};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01703,
CC ECO:0000269|PubMed:17927448, ECO:0000269|PubMed:18024585,
CC ECO:0000269|PubMed:18344567, ECO:0000269|PubMed:19132955,
CC ECO:0000269|PubMed:28869968}.
CC -!- INTERACTION:
CC P60752; P60752: msbA; NbExp=4; IntAct=EBI-556367, EBI-556367;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_01703, ECO:0000269|PubMed:12119303,
CC ECO:0000269|PubMed:15919996, ECO:0000269|PubMed:8809774}; Multi-pass
CC membrane protein {ECO:0000255|HAMAP-Rule:MF_01703,
CC ECO:0000269|PubMed:8809774}.
CC -!- DOMAIN: In MsbA the ATP-binding domain (NBD) and the transmembrane
CC domain (TMD) are fused. {ECO:0000269|PubMed:17927448,
CC ECO:0000269|PubMed:18024585}.
CC -!- DOMAIN: Substrate binding induces conformational changes, NBD
CC dimerization, and stabilizes an inward-facing closed pre-translocation
CC state that binds ATP (PubMed:18344567, PubMed:23766512,
CC PubMed:28869968). ATP binding fuels a relative motion of the NBD
CC domains. The movement of the NBDs is coupled to reorientation of the
CC chamber, which binds the lipid substrate, from cytoplasmic-facing to
CC periplasmic-facing through large amplitude motion on either side of the
CC transporter (PubMed:17927448, PubMed:20715055, PubMed:18024585,
CC PubMed:28869968). ATP hydrolysis is then required to resolve the
CC outward-facing conformation back to an inward-facing conformation
CC (PubMed:23766512, PubMed:28869968). The ATP-dependent switch requires
CC robust tetrahelix bundle interactions (PubMed:23306205).
CC {ECO:0000269|PubMed:17927448, ECO:0000269|PubMed:18024585,
CC ECO:0000269|PubMed:18344567, ECO:0000269|PubMed:20715055,
CC ECO:0000269|PubMed:23306205, ECO:0000269|PubMed:23766512,
CC ECO:0000269|PubMed:28869968}.
CC -!- DOMAIN: Contains two substrate-binding sites that communicate with both
CC the nucleotide-binding domain and with each other. One is a high
CC affinity binding site for the physiological substrate, lipid A, and the
CC other site interacts with drugs with comparable affinity.
CC {ECO:0000269|PubMed:19132955}.
CC -!- DISRUPTION PHENOTYPE: Absence of MsbA alone causes accumulation of
CC hexa-acylated lipid A species and glycerophospholipids in the inner
CC membrane. {ECO:0000269|PubMed:9575204}.
CC -!- MISCELLANEOUS: In addition to ATP hydrolysis, may utilize another major
CC energy currency in the cell by coupling substrate transport to a
CC transmembrane electrochemical proton gradient (PubMed:27499013). In
CC vitro, MsbA-mediated ethidium efflux is dependent on both the
CC electrochemical proton gradient and ATP hydrolysis (PubMed:27499013).
CC {ECO:0000269|PubMed:27499013}.
CC -!- MISCELLANEOUS: Identified as a drug target. Inhibited by a series of
CC quinoline compounds that kill E.coli through inhibition of ATPase and
CC transport activity of MsbA. {ECO:0000269|PubMed:30104274}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. Lipid exporter
CC (TC 3.A.1.106) family. {ECO:0000255|HAMAP-Rule:MF_01703}.
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DR EMBL; Z11796; CAA77839.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74000.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA35658.1; -; Genomic_DNA.
DR PIR; C85617; C85617.
DR PIR; E90753; E90753.
DR PIR; S27998; S27998.
DR RefSeq; NP_415434.1; NC_000913.3.
DR RefSeq; WP_000551270.1; NZ_STEB01000006.1.
DR PDB; 3B5W; X-ray; 5.30 A; A/B/C/D/E/F/G/H=1-582.
DR PDB; 6UZ2; EM; 4.20 A; A/B=1-582.
DR PDB; 6UZL; EM; 4.40 A; A/B=1-582.
DR PDB; 7BCW; EM; 3.50 A; A/B=1-582.
DR PDBsum; 3B5W; -.
DR PDBsum; 6UZ2; -.
DR PDBsum; 6UZL; -.
DR PDBsum; 7BCW; -.
DR AlphaFoldDB; P60752; -.
DR SASBDB; P60752; -.
DR SMR; P60752; -.
DR BioGRID; 4260013; 296.
DR ComplexPortal; CPX-2116; MsbA transporter complex.
DR DIP; DIP-36229N; -.
DR IntAct; P60752; 2.
DR STRING; 511145.b0914; -.
DR TCDB; 3.A.1.106.1; the atp-binding cassette (abc) superfamily.
DR jPOST; P60752; -.
DR PaxDb; P60752; -.
DR PRIDE; P60752; -.
DR EnsemblBacteria; AAC74000; AAC74000; b0914.
DR EnsemblBacteria; BAA35658; BAA35658; BAA35658.
DR GeneID; 66670810; -.
DR GeneID; 945530; -.
DR KEGG; ecj:JW0897; -.
DR KEGG; eco:b0914; -.
DR PATRIC; fig|1411691.4.peg.1362; -.
DR EchoBASE; EB0608; -.
DR eggNOG; COG1132; Bacteria.
DR HOGENOM; CLU_000604_84_3_6; -.
DR InParanoid; P60752; -.
DR OMA; WGTYLVK; -.
DR PhylomeDB; P60752; -.
DR BioCyc; EcoCyc:EG10613-MON; -.
DR BioCyc; MetaCyc:EG10613-MON; -.
DR BRENDA; 7.5.2.6; 2026.
DR BRENDA; 7.6.2.1; 2026.
DR SABIO-RK; P60752; -.
DR EvolutionaryTrace; P60752; -.
DR PRO; PR:P60752; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0043190; C:ATP-binding cassette (ABC) transporter complex; IDA:EcoCyc.
DR GO; GO:0005887; C:integral component of plasma membrane; ISM:EcoCyc.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:1990199; C:MsbA transporter complex; IPI:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IDA:EcoCyc.
DR GO; GO:0005524; F:ATP binding; IDA:EcoCyc.
DR GO; GO:0034040; F:ATPase-coupled lipid transmembrane transporter activity; IDA:EcoliWiki.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008289; F:lipid binding; IDA:EcoliWiki.
DR GO; GO:0015437; F:lipopolysaccharide floppase activity; IDA:EcoCyc.
DR GO; GO:0034204; P:lipid translocation; IDA:EcoCyc.
DR GO; GO:0006869; P:lipid transport; IMP:ComplexPortal.
DR GO; GO:0015920; P:lipopolysaccharide transport; IMP:ComplexPortal.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR011917; ABC_transpr_lipidA.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR TIGRFAMs; TIGR02203; MsbA_lipidA; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
DR PROSITE; PS51239; MSBA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell inner membrane; Cell membrane;
KW Lipid transport; Membrane; Nucleotide-binding; Reference proteome;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..582
FT /note="ATP-dependent lipid A-core flippase"
FT /id="PRO_0000092577"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01703"
FT TRANSMEM 140..162
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01703"
FT TRANSMEM 167..186
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01703"
FT TRANSMEM 253..273
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01703"
FT TRANSMEM 275..295
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01703"
FT DOMAIN 27..310
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01703"
FT DOMAIN 342..578
FT /note="ABC transporter"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01703"
FT BINDING 376..383
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01703"
FT MUTAGEN 88
FT /note="C->S: Does not affect ATPase activity."
FT /evidence="ECO:0000269|PubMed:19132955"
FT MUTAGEN 208
FT /note="E->A: Does not reduce substrate binding or
FT nucleotide binding, but decreases ATP-dependent extrusion
FT of substrates. Inhibits formation of outward-facing
FT conformation."
FT /evidence="ECO:0000269|PubMed:23306205"
FT MUTAGEN 208
FT /note="E->C: Exhibits ATPase activity. Forms intermolecular
FT cross-links."
FT /evidence="ECO:0000269|PubMed:20715055"
FT MUTAGEN 208
FT /note="E->Q: Improves basal ATPase activity and increases
FT transport activity."
FT /evidence="ECO:0000269|PubMed:23306205"
FT MUTAGEN 212
FT /note="K->A: Does not reduce substrate binding or
FT nucleotide binding, but decreases ATP-dependent extrusion
FT of substrates."
FT /evidence="ECO:0000269|PubMed:23306205"
FT MUTAGEN 270
FT /note="A->T: Temperature-sensitive. Loss of lipid export to
FT the outer membrane. Significantly decreases ATPase activity
FT at 42 degrees Celsius but not at 30 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:11278265,
FT ECO:0000269|PubMed:12119303"
FT MUTAGEN 315
FT /note="C->S: Does not affect ATPase activity."
FT /evidence="ECO:0000269|PubMed:19132955"
FT MUTAGEN 506
FT /note="E->Q: Lacks cell viability and does not support
FT growth. Can still bind ATP and slowly hydrolyze ATP, but
FT becomes locked into a closed dimer conformation."
FT /evidence="ECO:0000269|PubMed:21462989"
FT MUTAGEN 511
FT /note="L->P: Loss of ATPase activity; ATP is still bound."
FT /evidence="ECO:0000269|PubMed:8809774"
FT MUTAGEN 512
FT /note="D->G: Loss of ATPase activity; ATP is still bound."
FT /evidence="ECO:0000269|PubMed:8809774"
FT MUTAGEN 537
FT /note="H->A: Lacks cell viability and does not support
FT growth. Can still bind ATP and slowly hydrolyze ATP, but
FT becomes locked into a closed dimer conformation."
FT /evidence="ECO:0000269|PubMed:21462989"
FT HELIX 11..20
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 21..24
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 25..45
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:7BCW"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 67..108
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 113..116
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 131..140
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 142..163
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 170..212
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 214..219
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 223..270
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 273..276
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 281..322
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 342..348
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 370..376
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 383..388
FT /evidence="ECO:0007829|PDB:7BCW"
FT TURN 389..391
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 396..402
FT /evidence="ECO:0007829|PDB:7BCW"
FT TURN 407..409
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 412..416
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 419..422
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 433..437
FT /evidence="ECO:0007829|PDB:7BCW"
FT TURN 442..444
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 447..456
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 460..463
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 469..471
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 483..486
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 489..496
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 500..506
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 509..511
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 513..526
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 528..535
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 546..552
FT /evidence="ECO:0007829|PDB:7BCW"
FT STRAND 555..560
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 562..566
FT /evidence="ECO:0007829|PDB:7BCW"
FT TURN 567..569
FT /evidence="ECO:0007829|PDB:7BCW"
FT HELIX 571..576
FT /evidence="ECO:0007829|PDB:7BCW"
SQ SEQUENCE 582 AA; 64461 MW; 3D52A3482174A7FE CRC64;
MHNDKDLSTW QTFRRLWPTI APFKAGLIVA GVALILNAAS DTFMLSLLKP LLDDGFGKTD
RSVLVWMPLV VIGLMILRGI TSYVSSYCIS WVSGKVVMTM RRRLFGHMMG MPVSFFDKQS
TGTLLSRITY DSEQVASSSS GALITVVREG ASIIGLFIMM FYYSWQLSII LIVLAPIVSI
AIRVVSKRFR NISKNMQNTM GQVTTSAEQM LKGHKEVLIF GGQEVETKRF DKVSNRMRLQ
GMKMVSASSI SDPIIQLIAS LALAFVLYAA SFPSVMDSLT AGTITVVFSS MIALMRPLKS
LTNVNAQFQR GMAACQTLFT ILDSEQEKDE GKRVIERATG DVEFRNVTFT YPGRDVPALR
NINLKIPAGK TVALVGRSGS GKSTIASLIT RFYDIDEGEI LMDGHDLREY TLASLRNQVA
LVSQNVHLFN DTVANNIAYA RTEQYSREQI EEAARMAYAM DFINKMDNGL DTVIGENGVL
LSGGQRQRIA IARALLRDSP ILILDEATSA LDTESERAIQ AALDELQKNR TSLVIAHRLS
TIEKADEIVV VEDGVIVERG THNDLLEHRG VYAQLHKMQF GQ
