MELB_SALTY
ID MELB_SALTY Reviewed; 476 AA.
AC P30878;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 3.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Melibiose permease {ECO:0000303|PubMed:1495487};
DE AltName: Full=Melibiose carrier;
DE AltName: Full=Melibiose transporter;
DE AltName: Full=Melibiose/cation symporter {ECO:0000305};
DE AltName: Full=Na+ (Li+)/melibiose symporter {ECO:0000303|PubMed:1495487};
DE AltName: Full=Thiomethylgalactoside permease II;
GN Name=melB {ECO:0000303|PubMed:1495487}; OrderedLocusNames=STM4299;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=LT2;
RX PubMed=1495487; DOI=10.1007/bf00272347;
RA Mizushima K., Awakihara S., Kuroda M., Ishikawa T., Tsuda M., Tsuchiya T.;
RT "Cloning and sequencing of the melB gene encoding the melibiose permease of
RT Salmonella typhimurium LT2.";
RL Mol. Gen. Genet. 234:74-80(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RC STRAIN=LT2;
RX PubMed=21148559; DOI=10.1074/jbc.m110.206227;
RA Guan L., Nurva S., Ankeshwarapu S.P.;
RT "Mechanism of melibiose/cation symport of the melibiose permease of
RT Salmonella typhimurium.";
RL J. Biol. Chem. 286:6367-6374(2011).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=29054867; DOI=10.1085/jgp.201711788;
RA Hariharan P., Guan L.;
RT "Thermodynamic cooperativity of cosubstrate binding and cation selectivity
RT of Salmonella typhimurium MelB.";
RL J. Gen. Physiol. 149:1029-1039(2017).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, ACTIVITY REGULATION, AND
RP DOMAIN.
RX PubMed=34110360; DOI=10.1085/jgp.202012710;
RA Hariharan P., Guan L.;
RT "Cooperative binding ensures the obligatory melibiose/Na+ cotransport in
RT MelB.";
RL J. Gen. Physiol. 153:0-0(2021).
RN [6] {ECO:0007744|PDB:4M64}
RP X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS OF LYS-18; ASP-19; ARG-52;
RP ASP-55; ASN-58; ASP-59; TYR-120; THR-121; MET-123; ASP-124; TRP-128;
RP ARG-149 AND LYS-377.
RX PubMed=24389923; DOI=10.1038/ncomms4009;
RA Ethayathulla A.S., Yousef M.S., Amin A., Leblanc G., Kaback H.R., Guan L.;
RT "Structure-based mechanism for Na(+)/melibiose symport by MelB.";
RL Nat. Commun. 5:3009-3009(2014).
RN [7] {ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17}
RP X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) OF 2-476 OF MUTANT CYS-59 IN
RP COMPLEXES WITH NITROPHENYL-ALPHA-D-GALACTOSIDE AND
RP DODECYL-BETA-D-MELIBIOSIDE, SUBCELLULAR LOCATION, TOPOLOGY, AND DOMAIN.
RX PubMed=34341464; DOI=10.1038/s42003-021-02462-x;
RA Guan L., Hariharan P.;
RT "X-ray crystallography reveals molecular recognition mechanism for sugar
RT binding in a melibiose transporter MelB.";
RL Commun. Biol. 4:931-931(2021).
CC -!- FUNCTION: Mediates the transport of melibiose and other galactosides by
CC a symport mechanism (PubMed:21148559, PubMed:24389923, PubMed:29054867,
CC PubMed:34110360). Can use sodium, lithium and protons as coupling
CC cations, with a preference for sodium and lithium (PubMed:21148559,
CC PubMed:24389923, PubMed:29054867). The use of Na(+) as coupling ion for
CC sugar transport is based not on ion selectivity but on competitive
CC binding under physiological conditions, because of a much higher Na(+)
CC concentration under physiological conditions (PubMed:29054867).
CC {ECO:0000269|PubMed:21148559, ECO:0000269|PubMed:24389923,
CC ECO:0000269|PubMed:29054867, ECO:0000269|PubMed:34110360}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=melibiose(in) + Na(+)(in) = melibiose(out) + Na(+)(out);
CC Xref=Rhea:RHEA:28851, ChEBI:CHEBI:28053, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:21148559, ECO:0000269|PubMed:24389923,
CC ECO:0000269|PubMed:29054867, ECO:0000269|PubMed:34110360};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Li(+)(in) + melibiose(in) = Li(+)(out) + melibiose(out);
CC Xref=Rhea:RHEA:28847, ChEBI:CHEBI:28053, ChEBI:CHEBI:49713;
CC Evidence={ECO:0000269|PubMed:21148559, ECO:0000269|PubMed:24389923};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) + melibiose(in) = H(+)(out) + melibiose(out);
CC Xref=Rhea:RHEA:28855, ChEBI:CHEBI:15378, ChEBI:CHEBI:28053;
CC Evidence={ECO:0000269|PubMed:21148559, ECO:0000269|PubMed:24389923,
CC ECO:0000269|PubMed:29054867};
CC -!- ACTIVITY REGULATION: Binding of Na(+) and melibiose is cooperative, the
CC binding affinity for one substrate is increased by the presence of the
CC other (PubMed:29054867, PubMed:34110360). With binding of one substrate
CC (either Na(+) or melibiose), MelB favors open conformations (likely
CC outward facing), whereas the cooperative binding of both substrates
CC induces cavity closure. Thus, cooperative binding is the key that
CC regulates the alternating-access process and ensures the obligatory
CC cotransport as the core mechanism for symport (PubMed:34110360).
CC Melibiose uptake is inhibited by valinomycin (PubMed:21148559).
CC {ECO:0000269|PubMed:21148559, ECO:0000269|PubMed:29054867,
CC ECO:0000269|PubMed:34110360}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:24389923,
CC ECO:0000269|PubMed:34341464}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:24389923, ECO:0000269|PubMed:34341464}.
CC -!- DOMAIN: Apoprotein is apparently conformationally labile and readily
CC converts to different states, including inward-facing conformations for
CC substrate access (PubMed:34110360). Contains a conserved cation-binding
CC pocket, which directly connects to the sugar specificity pocket
CC (PubMed:34341464). {ECO:0000269|PubMed:34110360,
CC ECO:0000269|PubMed:34341464}.
CC -!- SIMILARITY: Belongs to the sodium:galactoside symporter (TC 2.A.2)
CC family. {ECO:0000305}.
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DR EMBL; X62101; CAA44011.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL23123.1; -; Genomic_DNA.
DR PIR; S23576; S23576.
DR RefSeq; NP_463164.1; NC_003197.2.
DR RefSeq; WP_000028075.1; NC_003197.2.
DR PDB; 4M64; X-ray; 3.35 A; A/B/C/D=1-476.
DR PDB; 7L16; X-ray; 3.15 A; A=2-476.
DR PDB; 7L17; X-ray; 3.05 A; A=2-476.
DR PDBsum; 4M64; -.
DR PDBsum; 7L16; -.
DR PDBsum; 7L17; -.
DR AlphaFoldDB; P30878; -.
DR SMR; P30878; -.
DR STRING; 99287.STM4299; -.
DR PaxDb; P30878; -.
DR EnsemblBacteria; AAL23123; AAL23123; STM4299.
DR GeneID; 1255825; -.
DR KEGG; stm:STM4299; -.
DR PATRIC; fig|99287.12.peg.4521; -.
DR HOGENOM; CLU_027408_0_3_6; -.
DR OMA; DIPYWSM; -.
DR PhylomeDB; P30878; -.
DR BioCyc; SENT99287:STM4299-MON; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0071702; P:organic substance transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IEA:InterPro.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR039672; MFS_2.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR001927; Na/Gal_symport.
DR InterPro; IPR018043; Na/Gal_symport_CS.
DR PANTHER; PTHR11328; PTHR11328; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00792; gph; 1.
DR PROSITE; PS00872; NA_GALACTOSIDE_SYMP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane; Membrane;
KW Reference proteome; Sugar transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..476
FT /note="Melibiose permease"
FT /id="PRO_0000170753"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 8..30
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 31..41
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 42..66
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 67..76
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 98..104
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 105..129
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 130..143
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 144..167
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 168..177
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 178..200
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 201..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 233..255
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 256..266
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 267..289
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 290..296
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 297..318
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 319..323
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 324..349
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 350..366
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 367..394
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 395..408
FT /note="Periplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TRANSMEM 409..431
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT TOPO_DOM 432..476
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L16, ECO:0007744|PDB:7L17"
FT BINDING 18..19
FT /ligand="an alpha-D-galactoside"
FT /ligand_id="ChEBI:CHEBI:46953"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L17"
FT BINDING 124
FT /ligand="an alpha-D-galactoside"
FT /ligand_id="ChEBI:CHEBI:46953"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L17"
FT BINDING 128
FT /ligand="an alpha-D-galactoside"
FT /ligand_id="ChEBI:CHEBI:46953"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L17"
FT BINDING 149
FT /ligand="an alpha-D-galactoside"
FT /ligand_id="ChEBI:CHEBI:46953"
FT /evidence="ECO:0000269|PubMed:34341464,
FT ECO:0007744|PDB:7L17"
FT MUTAGEN 18
FT /note="K->C: Loss of transporter activity."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 19
FT /note="D->C: Loss of transporter activity."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 52
FT /note="R->C: Retains weak activity with Na(+), Li(+) or
FT H(+)."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 55
FT /note="D->C: Alters cation selectivity. Retains a low level
FT of H(+)-coupled melibiose transport, but retains only a
FT weak activity with Na(+) or Li(+)."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 58
FT /note="N->C: Alters cation selectivity. Decreases H(+)- and
FT Na(+)-coupled activity, with little effect on Li(+)-coupled
FT melibiose transport."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 59
FT /note="D->C: Alters cation selectivity. Retains only a low
FT level of H(+)-coupled melibiose binding and active
FT transport, but Na(+) or Li(+) does not stimulate either
FT binding or transport."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 120
FT /note="Y->C: Loss of transporter activity."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 121
FT /note="T->C: Alters cation selectivity. Inhibits H(+)- and
FT Na(+)-coupled activity, with little effect on Li(+)-coupled
FT melibiose transport."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 123
FT /note="M->C: Does not affect transporter activity."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 124
FT /note="D->C: Alters cation selectivity. Loss of transporter
FT activity."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 128
FT /note="W->C: Loss of transporter activity."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 149
FT /note="R->C: Retains weak activity with Na(+), Li(+) or
FT H(+)."
FT /evidence="ECO:0000269|PubMed:24389923"
FT MUTAGEN 377
FT /note="K->C: Inhibits Na(+)- and Li(+)-coupled activity,
FT with little effect on H(+)-coupled melibiose transport."
FT /evidence="ECO:0000269|PubMed:24389923"
FT CONFLICT 109
FT /note="V -> G (in Ref. 1; CAA44011)"
FT /evidence="ECO:0000305"
FT HELIX 5..20
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 23..35
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 41..67
FT /evidence="ECO:0007829|PDB:7L17"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:4M64"
FT HELIX 77..95
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 96..99
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 102..128
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 130..134
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 138..144
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 146..170
FT /evidence="ECO:0007829|PDB:7L17"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 175..200
FT /evidence="ECO:0007829|PDB:7L17"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 231..259
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 267..284
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 286..292
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 295..318
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 324..360
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 365..394
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 404..432
FT /evidence="ECO:0007829|PDB:7L17"
FT HELIX 438..450
FT /evidence="ECO:0007829|PDB:7L17"
SQ SEQUENCE 476 AA; 52801 MW; 040516772A474628 CRC64;
MSISLTTKLS YGFGAFGKDF AIGIVYMYLM YYYTDVVGLS VGLVGTLFLV ARIWDAINDP
IMGWIVNATR SRWGKFKPWI LIGTLTNSLV LFLLFSAHLF EGTAQVVFVC VTYILWGMTY
TIMDIPFWSL VPTITLDKRE REQLVPFPRF FASLAGFVTA GITLPFVSYV GGADRGFGFQ
MFTLVLIAFF IASTIVTLRN VHEVYSSDNG VTAGRPHLTL KTIVGLIYKN DQLSCLLGMA
LAYNIASNII NGFAIYYFTY VIGDADLFPY YLSYAGAANL LTLIVFPRLV KMLSRRILWA
GASVMPVLSC AGLFAMALAD IHNAALIVAA GIFLNIGTAL FWVLQVIMVA DTVDYGEFKL
NIRCESIAYS VQTMVVKGGS AFAAFFIALV LGLIGYTPNV AQSAQTLQGM QFIMIVLPVL
FFMMTLVLYF RYYRLNGDML RKIQIHLLDK YRKTPPFVEQ PDSPAISVVA TSDVKA
