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TitleStructures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.
Journal, issue, pagesPLoS Biol, Vol. 22, Issue 10, Page e3002874, Year 2024
Publish dateOct 18, 2024
AuthorsRakesh Maharjan / Zhemin Zhang / Philip A Klenotic / William D Gregor / Marios L Tringides / Meng Cui / Georgiana E Purdy / Edward W Yu /
PubMed AbstractThe Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These ...The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins. Currently, there is no structural information available for the subclass associated with MmpL4 and MmpL5, transporters that play a critical role in iron homeostasis of the bacterium. Here, we report cryo-EM structures of the M. smegmatis MmpL4 and MmpL5 transporters to resolutions of 2.95 Å and 3.00 Å, respectively. These structures allow us to propose a plausible pathway for siderophore translocation via these 2 transporters, an essential step for iron acquisition that enables the survival and replication of the mycobacterium.
External linksPLoS Biol / PubMed:39423221 / PubMed Central
MethodsEM (single particle)
Resolution2.81 - 3.0 Å
Structure data

44167

9b43

EMDB-44167, PDB-9b43:
Mycolicibacterium smegmatis MmpL4 structure
Method: EM (single particle) / Resolution: 2.95 Å

44171

9b46

EMDB-44171, PDB-9b46:
Mycolicibacterium smegmatis MmpL5 structure
Method: EM (single particle) / Resolution: 3.0 Å

47097

9dp6

EMDB-47097, PDB-9dp6:
Mycolicibacterium smegmatis MmpL5-AcpM structure
Method: EM (single particle) / Resolution: 2.81 Å

Chemicals

ChemComp-PNS:
4'-PHOSPHOPANTETHEINE

Source
  • mycolicibacterium smegmatis (bacteria)
KeywordsTRANSPORT PROTEIN / Siderophore / MmpL4 / Mycolicibacterium smegmatis / MmpL5 / AcpM

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