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3.A.1.106.1
Phospholipid, LPS, lipid A and drug exporter, MsbA, which flips the substrate from the inner leaflet of the cytoplasmic membrane to the outer leaflet (Eckford and Sharom, 2010). MsbA also confers drug resistance to azidopine, daunomycin, vinblastine, Hoechst 33342 and ethidium (Reuter et al., 2003). Four x-ray structures, trapped in different conformations, two with and two without nucleotide, have been solved (Ward et al., 2007). They suggest an alternating accessibility mode of transport with major conformational changes.  The mechanism and conformational transitions have been discussed (Moradi and Tajkhorshid 2013).  MsbA is energized both by ATP hydrolysis and the H+ electrochemical gradient (Singh et al. 2016). Mi et al. 2017 used single-particle cryo-electron microscopy to elucidate the structures of lipid-nanodisc-embedded MsbA in three functional states. The 4.2 Å-resolution structure of the transmembrane domains of nucleotide-free MsbA revealed that LPS binds deeply inside MsbA at the height of the periplasmic leaflet. Two sub-nanometre-resolution structures of MsbA with ADP-vanadate and ADP revealed a closed and an inward-facing conformation, respectively. A  2.9 A resolution structure of MsbA in complex with G907, a selective small-molecule antagonist with bactericidal activity, revealed an unanticipated mechanism of ABC transporter inhibition. G907 traps MsbA in an inward-facing, lipopolysaccharide-bound conformation by wedging into an architecturally conserved transmembrane pocket. A second allosteric mechanism of antagonism occurs through structural and functional uncoupling of the nucleotide-binding domains (Ho et al. 2018). Coupled ATPase-adenylate kinase activity in ABC transporters including MsbA has been demonstrated (Kaur et al. 2016).

Accession Number:P60752
Protein Name:Lipid A export ATP-binding/permease protein MsbA aka B0914
Length:582
Molecular Weight:64461.00
Species:Escherichia coli [83333]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Cell inner membrane1 / Multi-pass membrane protein2
Substrate phospholipids, LPS, Lipid A, drugs

Cross database links:

Genevestigator: P60752
EchoBASE: EB0608
EcoGene: EG10613
eggNOG: COG1132
HEGENOM: HBG758042
DIP: DIP-36229N
RefSeq: AP_001544.1    NP_415434.1   
Entrez Gene ID: 945530   
Pfam: PF00664    PF00005   
BioCyc: EcoCyc:EG10613-MONOMER    ECOL168927:B0914-MONOMER   
KEGG: ecj:JW0897    eco:b0914   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0005524 F:ATP binding
GO:0005319 F:lipid transporter activity
GO:0015437 F:lipopolysaccharide-transporting ATPase acti...
GO:0006869 P:lipid transport
GO:0055085 P:transmembrane transport

References (11)

[1] “The essential Escherichia coli msbA gene, a multicopy suppressor of null mutations in the htrB gene, is related to the universally conserved family of ATP-dependent translocators.”  Karow M.L.et.al.   8094880
[2] “A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map.”  Oshima T.et.al.   8905232
[3] “The complete genome sequence of Escherichia coli K-12.”  Blattner F.R.et.al.   9278503
[4] “Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110.”  Hayashi K.et.al.   16738553
[5] “Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid A and phospholipid biosynthesis.”  Zhou Z.et.al.   9575204
[6] “ATPase activity of the MsbA lipid flippase of Escherichia coli.”  Doerrler W.T.et.al.   12119303
[7] “Mutational analysis and properties of the msbA gene of Escherichia coli, coding for an essential ABC family transporter.”  Polissi A.et.al.   8809774
[8] “An Escherichia coli mutant defective in lipid export.”  Doerrler W.T.et.al.   11278265
[9] “Global topology analysis of the Escherichia coli inner membrane proteome.”  Daley D.O.et.al.   15919996
[10] “Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters.”  Chang G.et.al.   11546864
[11] “”  Chang G.et.al.   17185584
Structure:
3B5W   3b5y     

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FASTA formatted sequence
1:	MHNDKDLSTW QTFRRLWPTI APFKAGLIVA GVALILNAAS DTFMLSLLKP LLDDGFGKTD 
61:	RSVLVWMPLV VIGLMILRGI TSYVSSYCIS WVSGKVVMTM RRRLFGHMMG MPVSFFDKQS 
121:	TGTLLSRITY DSEQVASSSS GALITVVREG ASIIGLFIMM FYYSWQLSII LIVLAPIVSI 
181:	AIRVVSKRFR NISKNMQNTM GQVTTSAEQM LKGHKEVLIF GGQEVETKRF DKVSNRMRLQ 
241:	GMKMVSASSI SDPIIQLIAS LALAFVLYAA SFPSVMDSLT AGTITVVFSS MIALMRPLKS 
301:	LTNVNAQFQR GMAACQTLFT ILDSEQEKDE GKRVIERATG DVEFRNVTFT YPGRDVPALR 
361:	NINLKIPAGK TVALVGRSGS GKSTIASLIT RFYDIDEGEI LMDGHDLREY TLASLRNQVA 
421:	LVSQNVHLFN DTVANNIAYA RTEQYSREQI EEAARMAYAM DFINKMDNGL DTVIGENGVL 
481:	LSGGQRQRIA IARALLRDSP ILILDEATSA LDTESERAIQ AALDELQKNR TSLVIAHRLS 
541:	TIEKADEIVV VEDGVIVERG THNDLLEHRG VYAQLHKMQF GQ