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==Cryo-EM structure of Mycobacterium smegmatis MmpL3 complexed with ST004 in lipid nanodiscs==
==Cryo-EM structure of Mycobacterium smegmatis MmpL3 complexed with ST004 in lipid nanodiscs==
<StructureSection load='7wnx' size='340' side='right'caption='[[7wnx]]' scene=''>
<StructureSection load='7wnx' size='340' side='right'caption='[[7wnx]], [[Resolution|resolution]] 3.36&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WNX FirstGlance]. <br>
<table><tr><td colspan='2'>[[7wnx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WNX FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wnx OCA], [https://pdbe.org/7wnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wnx RCSB], [https://www.ebi.ac.uk/pdbsum/7wnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wnx ProSAT]</span></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1I2:N-[2-(2-adamantylamino)ethyl]-1-[2,4-bis(fluoranyl)phenyl]-5-(4-chlorophenyl)-4-methyl-pyrazole-3-carboxamide'>1I2</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wnx OCA], [https://pdbe.org/7wnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wnx RCSB], [https://www.ebi.ac.uk/pdbsum/7wnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wnx ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/MMPL3_MYCS2 MMPL3_MYCS2]] Transports trehalose monomycolate (TMM) to the cell wall (PubMed:31239378, PubMed:22520756, PubMed:28698380). Flips TMM across the inner membrane. Membrane potential is not required for this function (PubMed:28698380). Transports probably phosphatidylethanolamine (PE) as well. Binds specifically both TMM and PE, but not trehalose dimycolate (TDM). Binds also diacylglycerol (DAG) and other phospholipids, including phosphatidylglycerol (PG), phosphatidylinositol (PI), and cardiolipin (CDL) (PubMed:31113875). Contributes to membrane potential, cell wall composition, antibiotic susceptibility and fitness (PubMed:28703701).<ref>PMID:22520756</ref> <ref>PMID:28698380</ref> <ref>PMID:28703701</ref> <ref>PMID:31113875</ref> <ref>PMID:31239378</ref>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis MC2 155]]
[[Category: Hu T]]
[[Category: Hu T]]
[[Category: Liu F]]
[[Category: Liu F]]

Revision as of 06:22, 8 September 2022

Cryo-EM structure of Mycobacterium smegmatis MmpL3 complexed with ST004 in lipid nanodiscsCryo-EM structure of Mycobacterium smegmatis MmpL3 complexed with ST004 in lipid nanodiscs

Structural highlights

7wnx is a 1 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MMPL3_MYCS2] Transports trehalose monomycolate (TMM) to the cell wall (PubMed:31239378, PubMed:22520756, PubMed:28698380). Flips TMM across the inner membrane. Membrane potential is not required for this function (PubMed:28698380). Transports probably phosphatidylethanolamine (PE) as well. Binds specifically both TMM and PE, but not trehalose dimycolate (TDM). Binds also diacylglycerol (DAG) and other phospholipids, including phosphatidylglycerol (PG), phosphatidylinositol (PI), and cardiolipin (CDL) (PubMed:31113875). Contributes to membrane potential, cell wall composition, antibiotic susceptibility and fitness (PubMed:28703701).[1] [2] [3] [4] [5]

References

  1. ↑ Varela C, Rittmann D, Singh A, Krumbach K, Bhatt K, Eggeling L, Besra GS, Bhatt A. MmpL genes are associated with mycolic acid metabolism in mycobacteria and corynebacteria. Chem Biol. 2012 Apr 20;19(4):498-506. doi: 10.1016/j.chembiol.2012.03.006. PMID:22520756 doi:http://dx.doi.org/10.1016/j.chembiol.2012.03.006
  2. ↑ Xu Z, Meshcheryakov VA, Poce G, Chng SS. MmpL3 is the flippase for mycolic acids in mycobacteria. Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):7993-7998. doi:, 10.1073/pnas.1700062114. Epub 2017 Jul 11. PMID:28698380 doi:http://dx.doi.org/10.1073/pnas.1700062114
  3. ↑ McNeil MB, Dennison D, Parish T. Mutations in MmpL3 alter membrane potential, hydrophobicity and antibiotic susceptibility in Mycobacterium smegmatis. Microbiology (Reading). 2017 Jul;163(7):1065-1070. doi: 10.1099/mic.0.000498., Epub 2017 Jul 21. PMID:28703701 doi:http://dx.doi.org/10.1099/mic.0.000498
  4. ↑ Su CC, Klenotic PA, Bolla JR, Purdy GE, Robinson CV, Yu EW. MmpL3 is a lipid transporter that binds trehalose monomycolate and phosphatidylethanolamine. Proc Natl Acad Sci U S A. 2019 May 21. pii: 1901346116. doi:, 10.1073/pnas.1901346116. PMID:31113875 doi:http://dx.doi.org/10.1073/pnas.1901346116
  5. ↑ Fay A, Czudnochowski N, Rock JM, Johnson JR, Krogan NJ, Rosenberg O, Glickman MS. Two Accessory Proteins Govern MmpL3 Mycolic Acid Transport in Mycobacteria. mBio. 2019 Jun 25;10(3). pii: mBio.00850-19. doi: 10.1128/mBio.00850-19. PMID:31239378 doi:http://dx.doi.org/10.1128/mBio.00850-19

7wnx, resolution 3.36Å

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