Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40802754.
- Also identified by DOI 10.1126/sciadv.adx1129 and PMC identifier 12346298.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
We coexpressed the mycobacterial membrane protein large 5 (MmpL5) transporter and MmpS5 adaptor proteins in <i>Mycobacterium smegmatis</i> 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 <i>M. smegmatis</i> 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.
Medical subject headings
- Mycobacterium smegmatis
- Bacterial Proteins
- Membrane Transport Proteins