MsbAAの輸送サイクルにおけるエネルギー伝導の構造的基礎

Jinhui Dong¹, Guangyong Yang, Hassane S McHaourab

¹Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.

Science (New York, N.Y.)

|May 14, 2005

まとめ

この研究では,マルチドラッグトランスポーターMsbAがATPを使って基板を移動する方法を明らかにし,耐性細胞に薬物流出を誘発する形状の変化を詳細に説明しています.

科学分野:

バイオケミストリーバイオケミストリー
構造生物学構造生物学とは
分子生物物理学分子生物物理学

背景:

多剤耐性ATP結合カセット (MDR ABC) トランスポーターは,薬物流出において極めて重要です.
輸送メカニズムを理解することは,多剤耐性との闘いに不可欠です.

研究の目的:

マルチドラッグトランスポーター MsbA.の形状運動を特徴づけるために.
エネルギー支出と基板転移を結びつけるメカニズムを解明する.

主な方法:

サイト指向のスピンラベリング
電子パラマグネティック共振 (EPR) スペクトロスコピー
リポソームベースの機能分析

主要な成果:

リガンドのないMsbAは,結晶構造とは異なる形状を呈し,緩やかな包装と周回プラズマの水浸透性を有する.
アデノシントリフォスファート (ATP) 結合は,基板室の閉塞を誘導し,サイトプラズマに結合し,周回プラズマ水分化を増加させます.
ATPの水解は,室内の介電環境と幾何学の変化を強調し,基板の転覆と退出を促します.

結論:

この研究は,MDR ABCトランスポーターにおけるパワーストロックの構造的動的基礎を確立しています.
これらの発見は,MsbA.A.の交替アクセスメカニズムについての洞察を提供します.
特定された形状の変化は,アンフィパシー基板の脱出のための潜在的な経路を提供します.

さらに関連する動画

09:53

High-Resolution Respirometry to Assess Bioenergetics in Cells and Tissues Using Chamber- and Plate-Based Respirometers

Published on: October 26, 2021

Assessing Energy Substrate Oxidation In Vitro with 14CO2 Trapping

09:20

Assessing Energy Substrate Oxidation In Vitro with ¹⁴CO₂ Trapping

Published on: March 23, 2022

関連する概念動画

01:32

Chemiosmosis

Oxidative phosphorylation is a highly efficient process that generates large amounts of adenosine triphosphate (ATP), the basic unit of energy that drives many cellular processes. Oxidative phosphorylation involves two processes— the electron transport chain and chemiosmosis.
Electron Transport Chain
The electron transport chain involves a series of protein complexes on the inner mitochondrial membrane that undergo a series of redox reactions. At the end of this chain, the electrons reduce...

01:34

The Z-Scheme of Electron Transport in Photosynthesis

The light reactions of photosynthesis assume a linear flow of electrons from water to NADP+. During this process, light energy drives the splitting of water molecules to produce oxygen. However, oxidation of water molecules is a thermodynamically unfavorable reaction and requires a strong oxidizing agent. This is accomplished by the first product of light reactions: oxidized P680 (or P680+), the most powerful oxidizing agent known in biology. The oxidized P680 that acquires an electron from the...

01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...

01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...

01:29

Electron Transport Chain Components

The electron transport chain (ETC) is a crucial metabolic pathway that facilitates energy conversion in prokaryotic and eukaryotic cells. In eukaryotes, the ETC comprises four membrane-associated protein complexes in the inner mitochondrial membrane. In prokaryotes, the ETC in the plasma membrane can vary in composition, with fewer or different complexes depending on the organism and environmental conditions. These complexes transfer electrons from electron donors, such as NADH and FADH2, to...

01:22

Chemiosmosis and ATP Synthesis

The electron transport chain is a critical component of cellular respiration, occurring in the inner mitochondrial membrane. It facilitates the transfer of high-energy electrons from reduced cofactors NADH and FADH₂ to molecular oxygen, the final electron acceptor. This transfer of electrons through a series of protein complexes is tightly coupled to the translocation of protons across the membrane, generating a proton gradient essential for ATP synthesis.Electron Flow and Proton...

関連する実験動画