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Title | Structural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation. |
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Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 3404, Year 2024 |
Publish date | Apr 22, 2024 |
Authors | Pingfeng Zhang / Zheng Liu / |
PubMed Abstract | DltB, a model member of the Membrane-Bound O-AcylTransferase (MBOAT) superfamily, plays a crucial role in D-alanylation of the lipoteichoic acid (LTA), a significant component of the cell wall of ...DltB, a model member of the Membrane-Bound O-AcylTransferase (MBOAT) superfamily, plays a crucial role in D-alanylation of the lipoteichoic acid (LTA), a significant component of the cell wall of gram-positive bacteria. This process stabilizes the cell wall structure, influences bacterial virulence, and modulates the host immune response. Despite its significance, the role of DltB is not well understood. Through biochemical analysis and cryo-EM imaging, we discover that Streptococcus thermophilus DltB forms a homo-tetramer on the cell membrane. We further visualize DltB in an apo form, in complex with DltC, and in complex with its inhibitor amsacrine (m-AMSA). Each tetramer features a central hole. The C-tunnel of each protomer faces the intratetramer interface and provides access to the periphery membrane. Each protomer binds a DltC without changing the tetrameric organization. A phosphatidylglycerol (PG) molecule in the substrate-binding site may serve as an LTA carrier. The inhibitor m-AMSA bound to the L-tunnel of each protomer blocks the active site. The tetrameric organization of DltB provides a scaffold for catalyzing D-alanyl transfer and regulating the channel opening and closing. Our findings unveil DltB's dual function in the D-alanylation pathway, and provide insight for targeting DltB as a anti-virulence antibiotic. |
External links | Nat Commun / PubMed:38649359 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.23 - 3.5 Å |
Structure data | EMDB-36192, PDB-8jem: EMDB-36194, PDB-8jes: EMDB-36207, PDB-8jf2: |
Chemicals | ChemComp-ASW: ChemComp-PGT: ChemComp-LMT: ChemComp-DGA: |
Source |
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Keywords | MEMBRANE PROTEIN/INHIBITOR / channel; anti-virulence; MBOAT; DltB / MEMBRANE PROTEIN / MEMBRANE PROTEIN-INHIBITOR complex / channel / anti-virulence / MBOAT / DltB / DltB; DltC |