9RSJ

Cryo-EM structure of MATE transporter NorM-VC in complex with doxorubicin

Summary for 9RSJ

• Entry DOI: 10.2210/pdb9rsj/pdb
• Related: 7PHP
• EMDB information: 54220
• Descriptor: Multidrug resistance protein NorM, NabFab HC, NabFab LC, ... (6 entities in total)
• Functional Keywords: nabfab, substrate, multidrug transporter, transport protein
• Biological source: Vibrio cholerae; More
• Total number of polymer chains: 5
• Total formula weight: 127126.72

Authors

Romane, K.,Hsieh, P.Y.,Kowal, J.,Locher, K.P.,van Veen, H.W. (deposition date: 2025-07-01, release date: 2025-11-26, Last modification date: 2025-12-10)

Primary citation

Hsieh, P.Y.,Romane, K.,Kowal, J.,Locher, K.P.,van Veen, H.W.
Doxorubicin Recognition and Transport by the MATE Multidrug Transporter NorM From Vibrio cholerae.
J.Mol.Biol., 438:169549-169549, 2025

PubMed Abstract: Multidrug and toxic compound extrusion (MATE) transport proteins contribute to multidrug resistance in human pathogens by extruding various cytotoxic compounds from the cellular interior. Despite their importance across all domains of life, the specificities and mechanisms of substrate transport of these proteins remain poorly understood due to limited structural and functional information. Here, we determined the cryo-electron microscopy structure of NorM from Vibrio cholerae (NorM-VC) in complex with the anthracycline antibiotic doxorubicin, using the NabFab approach. The structure reveals that the doxorubicin-binding pocket is located halfway through the membrane, within the C-lobe of the protein. Functional studies targeting the doxorubicin-interacting residues validated the binding pocket and enabled detailed analysis of the doxorubicin transport reaction. Our findings indicate doxorubicin binding within a multisite binding chamber engaged in a general transport mechanism for a variety of substrates.

PubMed: 41260293
DOI: 10.1016/j.jmb.2025.169549

Experimental method

ELECTRON MICROSCOPY (3.1 Å)