6ZY4

Cryo-EM structure of MlaFEDB in complex with ADP

6ZY4 の概要

• エントリーDOI: 10.2210/pdb6zy4/pdb
• 関連するPDBエントリー: 6zy2 6zy3
• EMDBエントリー: 11549
• 分子名称: YrbD protein, ABC transporter maintaining OM lipid asymmetry, cytoplasmic STAS component, Toluene tolerance protein Ttg2A, ... (6 entities in total)
• 機能のキーワード: phospholipid, phospholipid transport, abc transporter, mlafedb, mlafe, mlad, mlae, mlaf, mlab, outer membrane, mla transport pathway, lipid transport
• 由来する生物種: Escherichia coli B185; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 256080.71

構造登録者

Dong, C.J.,Dong, H.H. (登録日: 2020-07-30, 公開日: 2020-11-25, 最終更新日: 2024-05-01)

主引用文献

Tang, X.,Chang, S.,Qiao, W.,Luo, Q.,Chen, Y.,Jia, Z.,Coleman, J.,Zhang, K.,Wang, T.,Zhang, Z.,Zhang, C.,Zhu, X.,Wei, X.,Dong, C.,Zhang, X.,Dong, H.
Structural insights into outer membrane asymmetry maintenance in Gram-negative bacteria by MlaFEDB.
Nat.Struct.Mol.Biol., 28:81-91, 2021

PubMed Abstract: The highly asymmetric outer membrane of Gram-negative bacteria functions in the defense against cytotoxic substances, such as antibiotics. The Mla pathway maintains outer membrane lipid asymmetry by transporting phospholipids between the inner and outer membranes. It comprises six Mla proteins, MlaFEDBCA, including the ABC transporter MlaFEDB, which functions via an unknown mechanism. Here we determine cryo-EM structures of Escherichia coli MlaFEDB in an apo state and bound to phospholipid, ADP or AMP-PNP to a resolution of 3.3-4.1 Å and establish a proteoliposome-based transport system that includes MlaFEDB, MlaC and MlaA-OmpF to monitor the transport direction of phospholipids. In vitro transport assays and in vivo membrane permeability assays combined with mutagenesis identify functional residues that not only recognize and transport phospholipids but also regulate the activity and structural stability of the MlaFEDB complex. Our results provide mechanistic insights into the Mla pathway, which could aid antimicrobial drug development.

PubMed: 33199922
DOI: 10.1038/s41594-020-00532-y

実験手法

ELECTRON MICROSCOPY (4.1 Å)