8JF2

Cryo-EM structure of tetrameric DltB/DltC complex

8JF2 の概要

• エントリーDOI: 10.2210/pdb8jf2/pdb
• 関連するPDBエントリー: 8JEM
• EMDBエントリー: 36207
• 分子名称: Teichoic acid D-alanyltransferase, D-alanyl carrier protein, (1S)-2-{[{[(2R)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE, ... (5 entities in total)
• 機能のキーワード: channel, mboat, dltb; dltc, membrane protein
• 由来する生物種: Streptococcus thermophilus LMG 18311; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 261541.73

構造登録者

Zhang, P.,Liu, Z. (登録日: 2023-05-17, 公開日: 2024-05-22, 最終更新日: 2025-03-12)

主引用文献

Zhang, P.,Liu, Z.
Structural insights into the transporting and catalyzing mechanism of DltB in LTA D-alanylation.
Nat Commun, 15:3404-3404, 2024

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 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.

PubMed: 38649359
DOI: 10.1038/s41467-024-47783-7

実験手法

ELECTRON MICROSCOPY (3.5 Å)