人体抗原トランスポーターオルトログTmrABにおけるコンフォーマショナルカップリングとトランス阻害が二極EPRスペクトロシーで解明された
Katja Barth1, Susanne Hank2, Philipp E Spindler1
1Institute of Physical and Theoretical Chemistry , Goethe University Frankfurt , Max-von-Laue-Str. 7 , 60438 Frankfurt/Main , Germany.
Journal of the American Chemical Society
|January 9, 2018
まとめ
この研究では,ATP結合カセット (ABC) エクスポーターにおける非対称な核酸結合部位 (NBS) がトランスポーター機能を調節し,基板誘発阻害を説明しています. 医学的に重要なトランスポーターを理解するための枠組みを提供する.
科学分野:
- 膜タンパク質の生理学
- 構造生物学
- 生物化学
背景:
- ATP結合カセット (ABC) エクスポーターは,様々な基質の輸送に関与する重要な膜タンパク質です.
- 機能不全のABCエクスポートは 様々な人間の病気と関連しています
- ABCエクスポーターにおける非対称な核酸結合部位 (NBS) と基板誘発阻害の機能的意義は十分に理解されていません.
研究 の 目的:
- ABCの輸出者における触媒的非対称性の機能的関連性を調査する.
- 基質誘発トランス阻害のメカニズムを解明する.
- TmrABトランスポーターの構成動態を特徴づける.
主な方法:
- 先進的な電子-電子二重共振 (DEER) スペクトロスコピーを用いた.
- この研究は,ヒト抗原転移複合体TAPの同型であるTmrABに焦点を当てた.
- 構成バランスとドメインの相互依存性が分析された.
主要な成果:
- TmrABは,ATPの存在下で,内向きと外向きの形状の間の調整可能な均衡状態に存在する.
- この2つのNBSは,開閉のバランスにおいて有意な非対称性を示しています.
- トランス・インヒビレーションは,外向き状態から閉ざされた状態への逆転を経由してメカニズム的に定義された.
結論:
- リバーシブルな形状の均衡は,ABCの輸出者の機能と規制において中心的な役割を果たします.
- 非対称なトランスポーターにおけるトランス阻害のためのメカニズム的枠組みが確立された.
- この研究は,大きな膜タンパク質複合体における均衡集団とそれらの相互依存を解決する可能性を実証している.
関連する概念動画
01:20Conformity
48.2K
Conformity is the change in a person’s behavior to go along with the group, even if that person does not agree with the group.
48.2K
01:17Electron Paramagnetic Resonance (EPR) Spectroscopy: Organic Radicals
3.5K
Ideally, an unpaired electron shows a single peak in the EPR spectrum due to the transition between the two spin energy states. However, coupling interactions can occur between the spins of the unpaired electron and any neighboring spin-active nuclei. This hyperfine coupling results in hyperfine splitting, where the EPR signal is split into multiplets. The signals split into 2nI + 1 peaks, where n is the number of equivalent nuclei and I is the nuclear spin. These splitting patterns provide...
3.5K
01:08NMR Spectroscopy: Spin–Spin Coupling
3.3K
The spin state of an NMR-active nucleus can have a slight effect on its immediate electronic environment. This effect propagates through the intervening bonds and affects the electronic environments of NMR-active nuclei up to three bonds away; occasionally, even farther. This phenomenon is called spin–spin coupling or J-coupling. Coupling interactions are mutual and result in small changes in the absorption frequencies of both nuclei involved. While nuclei of the same element are involved...
3.3K
01:19Facilitated Transport
152.1K
The chemical and physical properties of plasma membranes cause them to be selectively permeable. Since plasma membranes have both hydrophobic and hydrophilic regions, substances need to be able to transverse both regions. The hydrophobic area of membranes repels substances such as charged ions. Therefore, such substances need special membrane proteins to cross a membrane successfully. In facilitated transport, also known as facilitated diffusion, molecules and ions travel across a...
152.1K
01:47Primary Active Transport
201.2K
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps that are embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction...
201.2K
02:22Regulated mRNA Transport
7.1K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
7.1K