View source for 9syj


==Asymmetric hexameric MmpS4-MmpL4 complex from Mycobacterium tuberculosis with "short" coiled-coil domain==
<StructureSection load='9syj' size='340' side='right'caption='[[9syj]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9syj]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9SYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SYJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.09&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</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=9syj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9syj OCA], [https://pdbe.org/9syj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9syj RCSB], [https://www.ebi.ac.uk/pdbsum/9syj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9syj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MMPL4_MYCTU MMPL4_MYCTU] Part of an export system, which is required for biosynthesis and secretion of siderophores (PubMed:23431276). Essential for normal replication during the active-growth phase of the murine tuberculosis model (PubMed:15908378).<ref>PMID:15908378</ref> <ref>PMID:23431276</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mycobacterium tuberculosis contains thirteen Mycobacterial membrane protein Large (MmpL) transporters, which belong to the family of secondary active RND transporters. MmpL4 and MmpL5, together with their operon partners MmpS4 and MmpS5, export the mycobacterial siderophore mycobactin and the last resort TB drug bedaquiline. Recently, we determined a structure of the MmpL4 monomer in complex with desferrated mycobactin, which lacked a functionally essential coiled-coil domain predicted to extend far into the periplasm. Here, we present a cryo-EM structure of the hexameric (MmpS4)(3)-(MmpL4)(3) complex, which was enabled by rational disulfide cross-links based on AlphaFold predictions. We observed density for the coiled-coil domain, which protrudes into the periplasmic space at an angle of around 60 degrees relative to the symmetry axis of the MmpL4 trimer. In the context of the hexameric complex, MmpL4's conformation differs strikingly from the one observed for monomeric MmpL4, which includes formation of a large cavity in the periplasmic domain and rearrangements of conserved proton coupling residues at the transmembrane domain. Our work provides an experimental workflow to obtain single particle cryo-EM structures of labile multiprotein complexes by AlphaFold-informed stabilization of predicted protein interfaces.

Structural elucidation of the hexameric MmpS4-MmpL4 complex from Mycobacterium tuberculosis.,Earp JC, Lichti NP, Garaeva AA, Meikle V, Niederweis M, Seeger MA bioRxiv [Preprint]. 2026 Jan 7:2026.01.07.698164. doi: , 10.64898/2026.01.07.698164. PMID:41542548<ref>PMID:41542548</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9syj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Earp JC]]
[[Category: Garaeva AA]]
[[Category: Lichti NP]]
[[Category: Seeger MA]]