第II型ミトコンドリアのNADH脱水生成への構造的洞察
1State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Nature
|October 23, 2012
まとめ
酵母NDI1は,II型NADH脱水酸化酵素 (NDH-2) で,ミトコンドリアの恒常性を維持し,複合I欠乏症疾患の治療の可能性を示しています. その結晶構造は,ホモディメリゼーションと,触媒作用に不可欠な二重ウビキノン結合部位を明らかにします.
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
- ミトコンドリア生理学 ミトコンドリア生理学
背景:
- タイプIIのNADH脱水酵素 (NDH-2s) は,ミトコンドリア呼吸器連鎖における複合体Iの重要な代替物である.
- 酵母NDH-2 (Ndi1) はミトコンドリアNADH/NAD(+) ホメオスタシスを維持し,パーキンソン病のような複合I欠乏症疾患の潜在的な治療薬です.
- 病原体内のNDH-2sは,新しい抗生物質の有望な標的である.
研究 の 目的:
- 酵母NDI1の結晶構造を決定することによって,NDH-2sの触媒メカニズムを解明する.
- Ndi1の活動,膜ターゲティング,基板結合の構造的基礎を理解する.
主な方法:
- X線結晶学を用いて,様々な基質結合状態におけるNDI1の構造を解明した.
- ホモディメリゼーションとユビキノン結合部位の役割を評価するために生化学的測定を用いた.
主要な成果:
- Ndi1のホモディメリゼーションは,触媒活性と膜局所化に不可欠である.
- 2つのユビキノン結合部位 (UQ ((I)) とUQ ((II)) が特定されました.
- NADHとUQ(I) は同時に結合することができ,UQ(I) はFAD経由でUQ(II) へ電子移転の中間体として作用する可能性が高い.
結論:
- この研究は,NDI1の調節および触媒メカニズムを明らかにした.
- これらの発見は,治療応用と抗生物質戦略のためのNDH-2sの開発とターゲティングを促進する可能性があります.
さらに関連する動画
08:37Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
Published on: June 1, 2017
06:53Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase (COX/SDH) Double-labeling Histochemistry
Published on: November 23, 2011
関連する概念動画
01:46Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
01:21Structure of Porins
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...
01:48ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
01:37Energy 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...
Generally, polypeptides are unfolded by two distinct...
01:43Electron Transport Chain: Complex III and IV
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
01:18ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...