9BD7

PaMsbA in an open, outward conformation

9BD7 の概要

• エントリーDOI: 10.2210/pdb9bd7/pdb
• EMDBエントリー: 44445
• 分子名称: ATP-dependent lipid A-core flippase, ZINC ION, ADP METAVANADATE, ... (4 entities in total)
• 機能のキーワード: msba, zinc, membrane protein, translocase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 135630.87

構造登録者

Bahramimoghaddam, H.,Laganowsky, A. (登録日: 2024-04-11, 公開日: 2025-09-03, 最終更新日: 2025-09-17)

主引用文献

Lyu, J.,Bahramimoghaddam, H.,Zhang, T.,Scott, E.,Yun, S.D.,Yadav, G.P.,Zhao, M.,Russell, D.,Laganowsky, A.
Molecular Basis for the Activation of Pseudomonas aeruginosa MsbA by Divalent Metals.
J.Am.Chem.Soc., 147:31488-31496, 2025

PubMed Abstract: Proteins involved in the biogenesis of lipopolysaccharide (LPS), a lipid exclusive to Gram-negative bacteria, are promising candidates for drug discovery. Specifically, the ABC transporter MsbA plays a crucial role in translocating an LPS precursor from the cytoplasmic to the periplasmic facing leaflet of the inner membrane, and small molecules that inhibit its function exhibit bactericidal activity. Here, we use native mass spectrometry (MS) to determine lipid binding affinities of MsbA from (PaMsbA), a Gram-negative bacteria associated with hospital-acquired infections, in different conformations. Unlike the transporter from , we show that the ATPase activity of PaMsbA is stimulated by Zn, Ni, and Mn and successfully trapping the protein with vanadate requires one of these metal ions. We also present cryogenic-electron microscopy structures of PaMsbA in occluded and open outward-facing conformations determined to resolutions of 2.58 and 2.44 Å, respectively. The structures reveal a triad of histidine residues, and mutation of these residues abolishes Zn binding and stimulation of PaMsbA activity by metal ions. Together, our studies provide insight into the structure of PaMsbA and its lipid binding preferences and reveal that a subset of divalent metals stimulates its ATPase activity.

PubMed: 40851428
DOI: 10.1021/jacs.4c18759

実験手法

ELECTRON MICROSCOPY (2.44 Å)