2.A.6.5.2
The lipid exporter, mycobacterial membrane protein Large-7, MmpL7, is required for the export of the virulence lipid, phthiocerol dimycocerosate (PDIM), in Mycobacterium tuberculosis. MmpL7. It also confers high level isoniazid efflux and resistance (Pasca et al., 2005). MmpL7 is also involved in the transport of the structurally related phenolic glycolipid (PGL). Moolla et al. 2021 generated an in silico model of MmpL7 that revealed MmpL7 as a functional outlier within the MmpL family, missing a canonical proton-relay signature sequence, suggesting that it employs a yet-unidentified mechanism for energy coupling for transport. The periplasmic porter domain 2 insert (PD2-insert), which doesn't share recognisable homology, is highly alpha-helical in nature, suggesting an organisation similar to that seen in the hopanoid PD3/4 domains. They also identified residues present in the transmembrane domains TM4 and TM10, and the PD2 domain insert that play crucial roles in PDIM transport (Moolla et al. 2021).
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| Accession Number: | P65370 |
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| Protein Name: | Putative membrane protein MML7 aka MmpL7 aka RV2942 aka MT3012 aka MTCY24G1.07C |
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| Length: | 920 |
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| Molecular Weight: | 95122.00 |
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| Species: | Mycobacterium tuberculosis [1773] |
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| Number of TMSs: | 12 |
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| Location1 / Topology2 / Orientation3: |
Cell membrane1 / Multi-pass membrane protein2 |
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| Substrate |
isoniazide |
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1: MPSPAGRLHR IRYIRLKKSS PDCRATITSG SADGQRRSPR LTNLLVVAAW VAAAVIANLL
61: LTFTQAEPHD TSPALLPQDA KTAAATSRIA QAFPGTGSNA IAYLVVEGGS TLEPQDQPYY
121: DAAVGALRAD TRHVGSVLDW WSDPVTAPLG TSPDGRSATA MVWLRGEAGT TQAAESLDAV
181: RSVLRQLPPS EGLRASIVVP AITNDMPMQI TAWQSATIVT VAAVIAVLLL LRARLSVRAA
241: AIVLLTADLS LAVAWPLAAV VRGHDWGTDS VFSWTLAAVL TIGTITAATM LAARLGSDAG
301: HSAAPTYRDS LPAFALPGAC VAIFTGPLLL ARTPALHGVG TAGLGVFVAL AASLTVLPAL
361: IALAGASRQL PAPTTGAGWT GRLSLPVSSA SALGTAAVLA ICMLPIIGMR WGVAENPTRQ
421: GGAQVLPGNA LPDVVVIKSA RDLRDPAALI AINQVSHRLV EVPGVRKVES AAWPAGVPWT
481: DASLSSAAGR LADQLGQQAG SFVPAVTAIK SMKSIIEQMS GAVDQLDSTV NVTLAGARQA
541: QQYLDPMLAA ARNLKNKTTE LSEYLETIHT WIVGFTNCPD DVLCTAMRKV IEPYDIVVTG
601: MNELSTGADR ISAISTQTMS ALSSAPRMVA QMRSALAQVR SFVPKLETTI QDAMPQIAQA
661: SAMLKNLSAD FADTGEGGFH LSRKDLADPS YRHVRESMFS SDGTATRLFL YSDGQLDLAA
721: AARAQQLEIA AGKAMKYGSL VDSQVTVGGA AQIAAAVRDA LIHDAVLLAV ILLTVVALAS
781: MWRGAVHGAA VGVGVLASYL AALGVSIALW QHLLDRELNA LVPLVSFAVL ASCGVPYLVA
841: GIKAGRIADE ATGARSKGAV SGRGAVAPLA ALGGVFGAGL VLVSGGSFSV LSQIGTVVVL
901: GLGVLITVQR AWLPTTPGRR