National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI145069
米国
引用
ジャーナル: PLoS Biol / 年: 2024 タイトル: Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition. 著者: Rakesh Maharjan / Zhemin Zhang / Philip A Klenotic / William D Gregor / Marios L Tringides / Meng Cui / Georgiana E Purdy / Edward W Yu / 要旨: 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 ...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.