LTAA_STAA8
ID LTAA_STAA8 Reviewed; 396 AA.
AC Q2FZP8;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Proton-coupled antiporter flippase LtaA {ECO:0000303|PubMed:32367070};
DE AltName: Full=Lipoteichoic acid protein A;
GN Name=ltaA {ECO:0000303|PubMed:17209021}; OrderedLocusNames=SAOUHSC_00952;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC 8325 / PS 47;
RA Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT "The Staphylococcus aureus NCTC 8325 genome.";
RL (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL D.C. (2006).
RN [2]
RP FUNCTION AS A PERMEASE, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=17209021; DOI=10.1128/jb.01683-06;
RA Gruendling A., Schneewind O.;
RT "Genes required for glycolipid synthesis and lipoteichoic acid anchoring in
RT Staphylococcus aureus.";
RL J. Bacteriol. 189:2521-2530(2007).
RN [3]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH UGTP AND LTAS.
RX PubMed=24533796; DOI=10.1111/mmi.12551;
RA Reichmann N.T., Picarra Cassona C., Monteiro J.M., Bottomley A.L.,
RA Corrigan R.M., Foster S.J., Pinho M.G., Gruendling A.;
RT "Differential localization of LTA synthesis proteins and their interaction
RT with the cell division machinery in Staphylococcus aureus.";
RL Mol. Microbiol. 92:273-286(2014).
RN [4]
RP PURIFICATION, CRYSTALLIZATION, AND SUBCELLULAR LOCATION.
RX PubMed=32112329; DOI=10.1007/978-1-0716-0373-4_19;
RA Zhang B., Perez C.;
RT "Stabilization and crystallization of a membrane protein involved in lipid
RT transport.";
RL Methods Mol. Biol. 2127:283-292(2020).
RN [5] {ECO:0007744|PDB:6S7V}
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 10-387, FUNCTION, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF GLU-26; ARG-29; ASP-62; TRP-121; TRP-144; TYR-314 AND
RP GLN-345.
RX PubMed=32367070; DOI=10.1038/s41594-020-0425-5;
RA Zhang B., Liu X., Lambert E., Mas G., Hiller S., Veening J.W., Perez C.;
RT "Structure of a proton-dependent lipid transporter involved in lipoteichoic
RT acids biosynthesis.";
RL Nat. Struct. Mol. Biol. 27:561-569(2020).
CC -!- FUNCTION: Proton-coupled antiporter flippase that catalyzes the
CC translocation, from the inner to the outer leaflet of the cell
CC membrane, of the lipid-linked disaccharide (anchor-LLD) that anchors
CC lipoteichoic acids (LTA) to the cell membrane (PubMed:32367070,
CC PubMed:17209021). Displays high selectivity towards the headgroup of
CC its substrate (PubMed:32367070). Plays an important role during
CC infection (PubMed:17209021). Contributes to S.aureus survival under
CC physiological acidic conditions (PubMed:32367070).
CC {ECO:0000269|PubMed:17209021, ECO:0000269|PubMed:32367070}.
CC -!- ACTIVITY REGULATION: Flipping activity is inhibited by increasing
CC concentrations of gentiobiose, a disaccharide with the same chemical
CC composition and conformation as the anchor-LLD headgroup. Not inhibited
CC by other disaccharides such as lactose, sucrose and trehalose at a
CC similar concentration. {ECO:0000269|PubMed:32367070}.
CC -!- PATHWAY: Cell wall biogenesis; lipoteichoic acid biosynthesis.
CC {ECO:0000269|PubMed:17209021}.
CC -!- SUBUNIT: Interacts with YpfP/UgtP, LtaS, and with numerous cell
CC division and peptidoglycan synthesis proteins.
CC {ECO:0000269|PubMed:24533796}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24533796,
CC ECO:0000269|PubMed:32112329, ECO:0000269|PubMed:32367070}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:32367070}. Note=Distributed all
CC around the membrane. {ECO:0000269|PubMed:24533796}.
CC -!- DOMAIN: The N-terminal hydrophilic pocket is crucial for flipping
CC activity. The central cavity of LtaA shows a unique amphiphilic
CC architecture. {ECO:0000269|PubMed:32367070}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant does not show a growth defect at
CC high pH, but it shows very strong growth retardation at low pH
CC (PubMed:32367070). At low pH, mutant displays aberrant cell
CC morphologies, including enlarged cells, defects in the formation and
CC localization of the division septum and abnormal cell-wall shape
CC (PubMed:32367070). Inactivation of the gene causes structural changes
CC in staphylococcal LTA but does not affect glycolipid synthesis
CC (PubMed:17209021). Mutants lacking this gene display a virulence defect
CC in a murine abscess model (PubMed:17209021).
CC {ECO:0000269|PubMed:17209021, ECO:0000269|PubMed:32367070}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. LtaA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABD30077.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; CP000253; ABD30077.1; ALT_INIT; Genomic_DNA.
DR RefSeq; WP_001154222.1; NZ_LS483365.1.
DR RefSeq; YP_499505.1; NC_007795.1.
DR PDB; 6S7V; X-ray; 3.30 A; A=10-387.
DR PDBsum; 6S7V; -.
DR AlphaFoldDB; Q2FZP8; -.
DR SMR; Q2FZP8; -.
DR STRING; 1280.SAXN108_1012; -.
DR TCDB; 2.A.1.2.44; the major facilitator superfamily (mfs).
DR EnsemblBacteria; ABD30077; ABD30077; SAOUHSC_00952.
DR GeneID; 3920663; -.
DR KEGG; sao:SAOUHSC_00952; -.
DR PATRIC; fig|93061.5.peg.873; -.
DR eggNOG; COG2814; Bacteria.
DR HOGENOM; CLU_054518_0_0_9; -.
DR BioCyc; MetaCyc:MON-20003; -.
DR UniPathway; UPA00556; -.
DR Proteomes; UP000008816; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0070395; P:lipoteichoic acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiport; Cell membrane; Lipid transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Virulence.
FT CHAIN 1..396
FT /note="Proton-coupled antiporter flippase LtaA"
FT /id="PRO_0000287159"
FT TOPO_DOM 1..14
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 15..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..45
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 46..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..79
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 80..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..104
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 105..126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 138..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..164
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 165..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..210
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..242
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 275..297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 298..302
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 303..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..369
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32367070"
FT TRANSMEM 370..390
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 391..396
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32367070"
FT MUTAGEN 26
FT /note="E->A: Flippase activity is about half that of wild-
FT type; when associated with A-62. Mutant is insensitive to
FT transmembrane proton gradients, maintaining basal activity.
FT Shows a strong growth defect at low pH. Cannot rescue the
FT growth defect of the deletion mutant in the presence of 5%
FT CO(2)."
FT /evidence="ECO:0000269|PubMed:32367070"
FT MUTAGEN 29
FT /note="R->A: Lack of flippase activity; when associated
FT with A-62. Cannot rescue the growth defect of the deletion
FT mutant in the presence of 5% CO(2). Can rescue the growth
FT defect under overexpression conditions."
FT /evidence="ECO:0000269|PubMed:32367070"
FT MUTAGEN 62
FT /note="D->A: Lack of flippase activity; when associated
FT with A-29. Flippase activity is about half that of wild-
FT type; when associated with A-26 or A-144. Cannot rescue the
FT growth defect of the deletion mutant in the presence of 5%
FT CO(2). Can rescue the growth defect under overexpression
FT conditions."
FT /evidence="ECO:0000269|PubMed:32367070"
FT MUTAGEN 121
FT /note="W->A: Cannot rescue the growth defect of the
FT deletion mutant in the presence of 5% CO(2). Can rescue the
FT growth defect under overexpression conditions."
FT /evidence="ECO:0000269|PubMed:32367070"
FT MUTAGEN 144
FT /note="W->A: Flippase activity is about half that of wild-
FT type; when associated with A-62. Cannot rescue the growth
FT defect of the deletion mutant in the presence of 5% CO(2).
FT Can rescue the growth defect under overexpression
FT conditions."
FT /evidence="ECO:0000269|PubMed:32367070"
FT MUTAGEN 314
FT /note="Y->A: Rescues the growth defect of the deletion
FT mutant in the presence of 5% CO(2)."
FT /evidence="ECO:0000269|PubMed:32367070"
FT MUTAGEN 345
FT /note="Q->A: Rescues the growth defect of the deletion
FT mutant in the presence of 5% CO(2)."
FT /evidence="ECO:0000269|PubMed:32367070"
FT HELIX 11..27
FT /evidence="ECO:0007829|PDB:6S7V"
FT TURN 28..35
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 36..43
FT /evidence="ECO:0007829|PDB:6S7V"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 50..74
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 79..98
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 103..126
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 136..159
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 164..167
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 168..182
FT /evidence="ECO:0007829|PDB:6S7V"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 200..209
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 214..224
FT /evidence="ECO:0007829|PDB:6S7V"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:6S7V"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:6S7V"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 247..266
FT /evidence="ECO:0007829|PDB:6S7V"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 277..294
FT /evidence="ECO:0007829|PDB:6S7V"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 300..328
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 334..359
FT /evidence="ECO:0007829|PDB:6S7V"
FT TURN 360..362
FT /evidence="ECO:0007829|PDB:6S7V"
FT HELIX 366..385
FT /evidence="ECO:0007829|PDB:6S7V"
SQ SEQUENCE 396 AA; 44618 MW; E9E525DFE9BBC7CC CRC64;
MQDSSLNNYA NHKNFILMLI ILFLMEFARG MYILSYINFL PTVTSIAVAI TSLAFSIHFI
ADASTNFVIG FLLKKFGTKI VLTTGFILAF TSLFLVIWFP ASPFVIIFSA MMLGIAVSPI
WVIMLSSVEE DKRGKQMGYV YFSWLLGLLV GMVFMNLLIK VHPTRFAFMM SLVVLIAWIL
YYFVDVKLTN YNTRPVKAQL RQIVDVTKRH LLLFPGILLQ GAAIAALVPI LPTYATKVIN
VSTIEYTVAI IIGGIGCAVS MLFLSKLIDN RSRNFMYGVI LSGFILYMIL IFTLSMIVNI
HILWIIALAI GLMYGILLPA WNTFMARFIK SDEQEETWGV FNSIQGFGSM IGPLFGGLIT
QFTNNLNNTF YFSALIFLVL AVFYGSYFIV NREKAK
