9QHJ

ATP-bound E178Q Wzm-Wzt from Mycobacterium abscessus in LMNG

Summary for 9QHJ

• Entry DOI: 10.2210/pdb9qhj/pdb
• Related: 9QFX 9QGU 9QH1 9QHK 9QHV 9QHW 9QHX
• EMDB information: 53123 53148 53152 53171
• Descriptor: ABC transporter permease, Probable o-antigen/lipopolysaccharide transport ATP-binding protein ABC transporter RfbE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: abc transporter type v abc transporter arabinogalactan precursor lipid-linked galactan exporter, membrane protein
• Biological source: Mycobacteroides abscessus; More
• Total number of polymer chains: 4
• Total formula weight: 129087.44

Authors

Garaeva, A.A.,Fabianova, V.,Savkova, K.,Huszar, S.,Xue, X.,Lowary, T.L.,Mikusova, K.,Seeger, M.A. (deposition date: 2025-03-15, release date: 2026-03-11, Last modification date: 2026-04-08)

Primary citation

Garaeva, A.A.,Fabianova, V.,Savkova, K.,Huszar, S.,Xue, X.,Lowary, T.L.,Mikusova, K.,Seeger, M.A.
Structural basis of lipid-linked galactan export by the mycobacterial ABC transporter Wzm-Wzt.
Nat Commun, 17:-, 2026

PubMed Abstract: Mycobacteria, including Mycobacterium tuberculosis, possess a unique cell envelope containing arabinogalactan, a heteropolysaccharide critical for cell wall integrity and target of several tuberculosis drugs. The cytosolic precursor of arabinogalactan, lipid-linked galactan (LLG), is translocated across the plasma membrane by the essential ABC transporter Wzm-Wzt through a molecular mechanism that is poorly understood. Here, we present a series of cryo-EM structures of Wzm-Wzt from Mycobacterium abscessus, representing different conformations of the transport cycle. Conserved residues lining the proposed LLG translocation pathway were investigated by three orthologous functional assays, revealing that the cytosolic gate helix (GH) plays a key functional role in polysaccharide transport. Our data suggests that the hydrophobic polyprenyl-moiety is translocated first, followed by the galactan-polysaccharide, which requires Wzm-Wzt to open a continuous channel through which the sugar chain is ratcheted at the expense of ATP hydrolysis. Our results provide a rational basis for the development of drugs that inhibit mycobacterial cell wall biosynthesis.

PubMed: 41839883
DOI: 10.1038/s41467-026-70429-9

Experimental method

ELECTRON MICROSCOPY (3.4 Å)