6NM1

The crystal structure of the Staphylococcus aureus Fatty acid Kinase (Fak) B1 protein A158L mutant to 2.33 Angstrom resolution exhibits a conformation change compared to the wild type form

6NM1 の概要

• エントリーDOI: 10.2210/pdb6nm1/pdb
• 関連するPDBエントリー: 5UTO 5WOO 6ALW 6B9I 6MH9
• 分子名称: Fatty acid Kinase (Fak) B1 protein, MYRISTIC ACID (3 entities in total)
• 機能のキーワード: staphylococcus aureus, fakb1, mutant, conformation change, transferase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64743.91

構造登録者

Cuypers, M.G.,Gullett, J.M.,Subramanian, C.,Ericson, M.,White, S.W.,Rock, C.O. (登録日: 2019-01-10, 公開日: 2020-01-15, 最終更新日: 2023-10-11)

主引用文献

Gullett, J.M.,Cuypers, M.G.,Grace, C.R.,Pant, S.,Subramanian, C.,Tajkhorshid, E.,Rock, C.O.,White, S.W.
Identification of structural transitions in bacterial fatty acid binding proteins that permit ligand entry and exit at membranes.
J.Biol.Chem., 298:101676-101676, 2022

PubMed Abstract: Fatty acid (FA) transfer proteins extract FA from membranes and sequester them to facilitate their movement through the cytosol. Detailed structural information is available for these soluble protein-FA complexes, but the structure of the protein conformation responsible for FA exchange at the membrane is unknown. Staphylococcus aureus FakB1 is a prototypical bacterial FA transfer protein that binds palmitate within a narrow, buried tunnel. Here, we define the conformational change from a "closed" FakB1 state to an "open" state that associates with the membrane and provides a path for entry and egress of the FA. Using NMR spectroscopy, we identified a conformationally flexible dynamic region in FakB1, and X-ray crystallography of FakB1 mutants captured the conformation of the open state. In addition, molecular dynamics simulations show that the new amphipathic α-helix formed in the open state inserts below the phosphate plane of the bilayer to create a diffusion channel for the hydrophobic FA tail to access the hydrocarbon core and place the carboxyl group at the phosphate layer. The membrane binding and catalytic properties of site-directed mutants were consistent with the proposed membrane docked structure predicted by our molecular dynamics simulations. Finally, the structure of the bilayer-associated conformation of FakB1 has local similarities with mammalian FA binding proteins and provides a conceptual framework for how these proteins interact with the membrane to create a diffusion channel from the FA location in the bilayer to the protein interior.

PubMed: 35122790
DOI: 10.1016/j.jbc.2022.101676

実験手法

X-RAY DIFFRACTION (2.33 Å)