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TitleStructures of MmpL complexes reveal the assembly and mechanism of this family of transporters.
Journal, issue, pagesSci Adv, Vol. 11, Issue 33, Page eadx1129, Year 2025
Publish dateAug 15, 2025
AuthorsZhemin Zhang / Rakesh Maharjan / William D Gregor / Philip A Klenotic / Edward W Yu /
PubMed AbstractWe coexpressed the mycobacterial membrane protein large 5 (MmpL5) transporter and MmpS5 adaptor proteins in and defined their structures from detergent-solubilized crude membranes. We observed that ...We coexpressed the mycobacterial membrane protein large 5 (MmpL5) transporter and MmpS5 adaptor proteins in and defined their structures from detergent-solubilized crude membranes. We observed that MmpL5 presents as a monomer in complex with the cytosolic meromycolate extension acyl carrier protein M (AcpM), where these AcpM-MmpL5 complexes generate regular two-dimensional arrays. We also provide structural information to show that MmpL5 assembles as a trimer that interacts with MmpS5 and AcpM to form the tripartite complex AcpM-MmpL5-MmpS5 that spans both the inner and outer membranes of the mycobacterium. In addition, we found that MmpL5 and AcpM are able to form the trimeric AcpM-MmpL5 complex. The structural data reveal that the full-length MmpL5 trimer is capable of spanning the entire mycobacterial cell envelope to transport substrates. However, this assembly requires the presence of MmpS5 to stabilize secondary structural features of the MmpL5 periplasmic subdomains.
External linksSci Adv / PubMed:40802754 / PubMed Central
MethodsEM (single particle)
Resolution2.81 - 3.67 Å
Structure data

48675

9mvz

EMDB-48675, PDB-9mvz:
Tripartite complex of MmpL5-S5-AcpM from Mycolicibacterium smegmatis
Method: EM (single particle) / Resolution: 2.81 Å

48676

9mw0

EMDB-48676, PDB-9mw0:
Bipartite complex of MmpL5-AcpM from Mycolicibacterium smegmatis
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-48701: Local refinement map of MmpL5-AcpM cluster part 1
Method: EM (single particle) / Resolution: 3.67 Å

EMDB-48702: Local refinement map of MmpL5-AcpM cluster part 3
Method: EM (single particle) / Resolution: 3.56 Å

EMDB-48703: The consensus map of MmpL5-AcpM cluster
Method: EM (single particle) / Resolution: 3.59 Å

EMDB-48704: Local refinement map of MmpL5-AcpM cluster part 2
Method: EM (single particle) / Resolution: 3.35 Å

48706

9mx0

EMDB-48706, PDB-9mx0:
Cluster of bipartite complex of MmpL5-AcpM from Mycolicibacterium smegmatis
Method: EM (single particle) / Resolution: 3.35 Å

Chemicals

ChemComp-PNS:
4'-PHOSPHOPANTETHEINE

Source
  • mycolicibacterium smegmatis (bacteria)
KeywordsMEMBRANE PROTEIN / MmpL5 / MmpS5 / AcpM / Tripartite complex / Mycolicibacterium smegmatis / bipartite complex

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