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Protein

Lipoarabinomannan carrier protein LprG

Gene

lprG

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probably helps membrane protein Rv1410c (P55) transport triacylglycerides (TAG) across the inner cell membrane into the periplasm; TAG probably regulates lipid metabolism and growth regulation (PubMed:26751071). Binds TAG and transfers it between lipid bilayers, probably to the outer membrane in vivo (PubMed:26751071). Binds di- and triacylated phosphatidyl-myo-inositol mannosides (PIMs), and glycolipid lipoglycan modulins lipoarabinomannan (LAM) and lipomannan (LM), facilitating their recognition by TLR2 (PubMed:20694006, PubMed:25356793). Binds LM > PIM6 > ManLAM > PI-LAM > PIM2 (mannose-capped LAM and phospho-myo-inositol-capped LAM, E.coli expressed without acyl-groups); deacylated LM and LAM also bind to this protein via their mannose moieties, showing LprG has at least 2 different ways to bind glycolipids (PubMed:25356793). Binds triacylglycerides (TAG) in the same cavity, is able to transfer TAG between lipid bilayers (PubMed:26751071). Overexpression of LprG and Rv1410c leads to increased levels of TAG in the culture medium (PubMed:26751071). Required for Rv1410c-mediated export of drugs (PubMed:18156250, PubMed:21762531). Required, probably with Rv1410c, for normal surface localization of LAM (PubMed:25232742).6 Publications
A host TLR2 agonist (toll-like receptor), shown experimentally for human and mouse (PubMed:19362712). Inhibits primary human macrophage MHC-II Ag processing via TLR2 (PubMed:15294983). Both lipidated and nonlipidated protein act as TLR2 agonists in antigen-presenting cells, although lipidated protein is more efficient (PubMed:20694006). In resting human CD4+ T-cells lipidated but not nonlipidated protein is a costimulatory ligand (with anti-CD3 and anti-CD28) for T-cell proliferation and IFN-gamma and IL-2 production, leading to increased expression of early T-cell activation markers, TLR2 and NFKB3 phosphorylation (PubMed:21078852). Human CD4+ T-cells use TLR1/TLR2 heterodimers to respond to this and probably other mycobacterial lipoproteins (PubMed:21078852). Able to stimulate proliferation of CD4+ T-cells derived from a human leprosy patient following protein processing/presentation by MHC class II molecules in peripheral blood mononuclear cells (PubMed:18424702). Requires both host TLR1 and TLR2 as coreceptors to elicit host response in mouse, although TLR6 may play a redundant role, has a partial requirement for CD14 as an accessory receptor (PubMed:19362712).5 Publications

Miscellaneous

Bacterial LAM blocks host cell phagosome-lysosome fusion and is one way in which M.tuberculosis evades the host immune system.2 Publications
Triacylglycerides accumulate in lipid droplets in the cytoplasm of M.tuberculosis stationary phase and dormant bacteria, and are used as an energy source during starvation (PubMed:26751071).1 Publication

GO - Molecular functioni

  • glycolipid binding Source: MTBBASE
  • phosphatidylinositol binding Source: UniProtKB

GO - Biological processi

  • lipid transport Source: UniProtKB-KW
  • pathogenesis Source: MTBBASE
  • response to antibiotic Source: UniProtKB-KW

Keywordsi

Biological processAntibiotic resistance, Lipid transport, Transport, Virulence
LigandLipid-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Lipoarabinomannan carrier protein LprG2 Publications
Alternative name(s):
27 kDa lipoprotein
Antigen P271 Publication
Lipoprotein LprG
Triacylated glycolipid carrier LprG1 Publication
Triacylglyceride transfer protein LprG1 Publication
Gene namesi
Name:lprG
Synonyms:lpp-27
Ordered Locus Names:Rv1411c
ORF Names:MTCY21B4.28c
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
Proteomesi
  • UP000001584 Componenti: Chromosome

Organism-specific databases

TubercuListiRv1411c.

Subcellular locationi

GO - Cellular componenti

  • bacterial extracellular vesicle Source: UniProtKB
  • cell surface Source: UniProtKB-SubCell
  • cell wall Source: MTBBASE
  • plasma membrane Source: MTBBASE

Keywords - Cellular componenti

Cell inner membrane, Cell membrane, Cell wall, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

A single deletion mutant leads to loss of expression of efflux pump Rv1410c due to polar effects; in infected BALB/c mice 1.5 and 2.5 log decrease in bacterial load 15 and 35 days after infection (PubMed:14998516). The single mutant increases sensitivity to malachite green, sodium dodecyl sulfate (SDS), isoniazid, ethambutal and ethidium bromide, alters the permeability of the cell wall; both genes of the operon are required to fully restore the phenotypes (PubMed:21762531). Single deletion mutant (probably without Rv1410c) has decreased surface-exposed glycolipid lipoarabinomannan (LAM), although cellular LAM, LM and PIM content is normal (PubMed:25232742, PubMed:25356793). Disruption of either Rv1410c or the lrpG-Rv1410c operon leads to increased levels of many triacylglyceride (TAG) alkylforms; up to 100-fold increase depending on the exact TAG form (PubMed:26751071). It also forms smaller colonies on agar (PubMed:25232742). Loss of surface LAM has several consequences; bacteria enter mouse macrophages with reduced efficiency and block mouse macrophage phagosome-lysosome fusion less efficiently than wild-type (PubMed:25232742). Reduced efficiency of mouse macrophage phagosome-lysosome fusion was seen in another study (PubMed:25356793). C57BL/6 mice infected with mutant bacteria have 10-fold less bacterial burden after 10 days and about 2700-fold less burden after 70 days; attenuation of mutant is not rescued in macrophages impaired for reactive oxygen or nitrogen generation (disruption of Ncf1 or iNOS) (PubMed:25232742).5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91V → W: Decreased TLR2 agonist activity, cannot acquire lipid from mycobacterial extracts, cavity entrance and size decrease. Binds PIM6, LM and ManLAM 10-100-fold less well than wild-type, binds de-acylated LM and ManLAM as well as wild-type. Decreased ability to transfer triacylglyceride between lipid bilayers. 3 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26PROSITE-ProRule annotationAdd BLAST26
ChainiPRO_000001814627 – 236Lipoarabinomannan carrier protein LprGPROSITE-ProRule annotationAdd BLAST210

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi27N-palmitoyl cysteinePROSITE-ProRule annotation1 Publication1
Lipidationi27S-diacylglycerol cysteinePROSITE-ProRule annotation1 Publication1

Post-translational modificationi

Modified by Lgt on Cys-27 with an S-linked diacylglyceral, signal peptide is removed by LspA, Cys-27 is further modifed with a fatty acid on its amino group by Lnt yielding a triacylated protein (Probable). Probably glycosylated, which is required for T-cell activation (PubMed:18424702).By similarity1 Publication1 Publication

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP9WK45.

Interactioni

Protein-protein interaction databases

STRINGi83332.Rv1411c.

Structurei

Secondary structure

1236
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi41 – 53Combined sources13
Beta strandi57 – 66Combined sources10
Beta strandi73 – 81Combined sources9
Turni82 – 85Combined sources4
Beta strandi86 – 95Combined sources10
Beta strandi98 – 107Combined sources10
Beta strandi110 – 116Combined sources7
Beta strandi119 – 125Combined sources7
Helixi126 – 128Combined sources3
Helixi132 – 135Combined sources4
Turni138 – 140Combined sources3
Helixi142 – 147Combined sources6
Beta strandi149 – 160Combined sources12
Beta strandi163 – 172Combined sources10
Helixi174 – 180Combined sources7
Helixi182 – 184Combined sources3
Beta strandi190 – 199Combined sources10
Beta strandi204 – 212Combined sources9
Beta strandi215 – 223Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MH8X-ray2.00A/B36-231[»]
3MH9X-ray1.79A/C28-236[»]
3MHAX-ray1.85A/B36-231[»]
4ZRAX-ray1.83A/C36-231[»]
ProteinModelPortaliP9WK45.
SMRiP9WK45.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni81 – 100Prevents bacterial uptake by a human macrophage-like cell line1 PublicationAdd BLAST20
Regioni141 – 160Prevents bacterial uptake by a human macrophage-like cell line1 PublicationAdd BLAST20
Regioni218 – 236Prevents bacterial uptake by a human macrophage-like cell line1 PublicationAdd BLAST19

Domaini

Forms a U-shaped beta-half-barrel with a small hydrophobic cavity (1500 Angstroms (3)) which holds a triacylated PIM in 1 crystal structure; the 3 acyl chains are within the cavity while the sugar moieties bind to the protein surface (PubMed:20694006). In the structure bound to triacylglycerides (TAG) 2 of the 3 acyl chains are buried in the cavity, the third is solvent exposed (PubMed:26751071). A flexible lid region may move to accommodate different TAG molecules (PubMed:26751071). Fragments of the mature protein (residues 81-100, 141-160 and 218-236) prevent uptake of M.tuberculosis by a human macrophage-like cell line; lesser effects are seen on bacterial uptake by a human lung epithelial cell line (PubMed:25041568).3 Publications

Sequence similaritiesi

Belongs to the LppX/LprAFG lipoprotein family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG41064B9. Bacteria.
ENOG4112A10. LUCA.
KOiK14954.
OMAiTLTPNKW.
PhylomeDBiP9WK45.

Family and domain databases

InterProiView protein in InterPro
IPR029046. LolA/LolB/LppX.
IPR009830. LppX/LprAFG.
PfamiView protein in Pfam
PF07161. LppX_LprAFG. 1 hit.
ProDomiView protein in ProDom or Entries sharing at least one domain
PD017293. DUF1396. 1 hit.
SUPFAMiSSF89392. SSF89392. 1 hit.
PROSITEiView protein in PROSITE
PS51257. PROKAR_LIPOPROTEIN. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P9WK45-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRTPRRHCRR IAVLAAVSIA ATVVAGCSSG SKPSGGPLPD AKPLVEEATA
60 70 80 90 100
QTKALKSAHM VLTVNGKIPG LSLKTLSGDL TTNPTAATGN VKLTLGGSDI
110 120 130 140 150
DADFVVFDGI LYATLTPNQW SDFGPAADIY DPAQVLNPDT GLANVLANFA
160 170 180 190 200
DAKAEGRDTI NGQNTIRISG KVSAQAVNQI APPFNATQPV PATVWIQETG
210 220 230
DHQLAQAQLD RGSGNSVQMT LSKWGEKVQV TKPPVS
Length:236
Mass (Da):24,548
Last modified:April 16, 2014 - v1
Checksum:i2591DAE6D2E2DC22
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP44170.1.
PIRiH70901.
RefSeqiNP_215927.1. NC_000962.3.
WP_003407315.1. NZ_KK339370.1.

Genome annotation databases

EnsemblBacteriaiCCP44170; CCP44170; Rv1411c.
GeneIDi886700.
KEGGimtu:Rv1411c.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA. Translation: CCP44170.1.
PIRiH70901.
RefSeqiNP_215927.1. NC_000962.3.
WP_003407315.1. NZ_KK339370.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MH8X-ray2.00A/B36-231[»]
3MH9X-ray1.79A/C28-236[»]
3MHAX-ray1.85A/B36-231[»]
4ZRAX-ray1.83A/C36-231[»]
ProteinModelPortaliP9WK45.
SMRiP9WK45.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi83332.Rv1411c.

Proteomic databases

PaxDbiP9WK45.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCCP44170; CCP44170; Rv1411c.
GeneIDi886700.
KEGGimtu:Rv1411c.

Organism-specific databases

TubercuListiRv1411c.

Phylogenomic databases

eggNOGiENOG41064B9. Bacteria.
ENOG4112A10. LUCA.
KOiK14954.
OMAiTLTPNKW.
PhylomeDBiP9WK45.

Family and domain databases

InterProiView protein in InterPro
IPR029046. LolA/LolB/LppX.
IPR009830. LppX/LprAFG.
PfamiView protein in Pfam
PF07161. LppX_LprAFG. 1 hit.
ProDomiView protein in ProDom or Entries sharing at least one domain
PD017293. DUF1396. 1 hit.
SUPFAMiSSF89392. SSF89392. 1 hit.
PROSITEiView protein in PROSITE
PS51257. PROKAR_LIPOPROTEIN. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiLPRG_MYCTU
AccessioniPrimary (citable) accession number: P9WK45
Secondary accession number(s): L0T868
, O32852, P0A5I8, P71679
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: March 15, 2017
This is version 27 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.