6JBH

Cryo-EM structure and transport mechanism of a wall teichoic acid ABC transporter

Summary for 6JBH

• Entry DOI: 10.2210/pdb6jbh/pdb
• EMDB information: 9790
• Descriptor: TarH, TarG (2 entities in total)
• Functional Keywords: abc transporter, transport protein
• Biological source: Alicyclobacillus herbarius; More
• Total number of polymer chains: 4
• Total formula weight: 126536.33

Authors

Chen, L.,Hou, W.T.,Fan, T.,Li, Y.H.,Liu, B.H.,Jiang, Y.L.,Sun, L.F.,Chen, Y.,Zhou, C.Z. (deposition date: 2019-01-25, release date: 2020-03-04, Last modification date: 2025-06-18)

Primary citation

Chen, L.,Hou, W.T.,Fan, T.,Liu, B.,Pan, T.,Li, Y.H.,Jiang, Y.L.,Wen, W.,Chen, Z.P.,Sun, L.,Zhou, C.Z.,Chen, Y.
Cryo-electron Microscopy Structure and Transport Mechanism of a Wall Teichoic Acid ABC Transporter.
Mbio, 11:-, 2020

PubMed Abstract: The wall teichoic acid (WTA) is a major cell wall component of Gram-positive bacteria, such as methicillin-resistant (MRSA), a common cause of fatal clinical infections in humans. Thus, the indispensable ABC transporter TarGH, which flips WTA from cytoplasm to extracellular space, becomes a promising target of anti-MRSA drugs. Here, we report the 3.9-Å cryo-electron microscopy (cryo-EM) structure of a 50% sequence-identical homolog of TarGH from at an ATP-free and inward-facing conformation. Structural analysis combined with activity assays enables us to clearly decode the binding site and inhibitory mechanism of the anti-MRSA inhibitor Targocil, which targets TarGH. Moreover, we propose a "crankshaft conrod" mechanism utilized by TarGH, which can be applied to similar ABC transporters that translocate a rather big substrate through relatively subtle conformational changes. These findings provide a structural basis for the rational design and optimization of antibiotics against MRSA. The wall teichoic acid (WTA) is a major component of cell wall and a pathogenic factor in methicillin-resistant (MRSA). The ABC transporter TarGH is indispensable for flipping WTA precursor from cytoplasm to the extracellular space, thus making it a promising drug target for anti-MRSA agents. The 3.9-Å cryo-EM structure of a TarGH homolog helps us to decode the binding site and inhibitory mechanism of a recently reported inhibitor, Targocil, and provides a structural platform for rational design and optimization of potential antibiotics. Moreover, we propose a "crankshaft conrod" mechanism to explain how a big substrate is translocated through subtle conformational changes of type II exporters. These findings advance our understanding of anti-MRSA drug design and ABC transporters.

PubMed: 32184247
DOI: 10.1128/mBio.02749-19

Experimental method

ELECTRON MICROSCOPY (3.94 Å)