ヒトのNav1.7チャネルの構造は,補助サブユニットと動物性毒素と複合している
Huaizong Shen1,2,3, Dongliang Liu1,2,3, Kun Wu4
1State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.
まとめ
痛みを和らげるための重要な標的である電圧ゲートされたナトリウムチャネルNav1.7の構造的な洞察は,冷凍電子顕微鏡を用いて明らかにされました. これらの発見は,新しい鎮痛剤の開発の道を開きます.
科学分野:
- 構造生物学
- 神経科学
- 薬理学について
背景:
- ボルテージゲートナトリウムチャネルNav1.7は,新しい疼痛緩和療法を開発するための重要なターゲットです.
- 効果的な鎮痛剤を設計するには 経路の構造を理解することが不可欠です
研究 の 目的:
- 毛穴遮断剤とゲーティング修正剤毒素 (GMT) に結合するヒトのNav1.7-β1-β2複合体の冷凍電子顕微鏡構造を決定する.
- Nav1.7 の機能と抑制の構造的基礎を解明する.
主な方法:
- 構造を決定するために,冷凍電子顕微鏡 (cryo-EM) が使用されました.
- この研究では,トトロドトキシンとプロトキシンII,サキシトキシンとフウエントキシンIVの2つの組み合わせを使用した.
主要な成果:
- Nav1.7複合体の高解像度 (3.2アングストーム) の構造が得られた.
- 構造は,電圧感知領域II (VSDII) と毒素結合部位のわずかなシフトでほぼ同一の形状を明らかにした.
- 観測された構造は,チャンネルの不活性状態を表す可能性があります.
結論:
- 決定された構造は,Nav1. 7チャンネル機能と阻害に関する前例のない洞察を提供します.
- これらの発見は,疼痛管理のためのNav1.7を標的とした構造支援薬の開発の基礎を築いた.
関連する概念動画
EDTA: Auxiliary Complexing Reagents
1.3K
EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...
1.3K
Animal and Plant Cell Structure
48.0K
Animal and plant cells not only differ in their structure, function, and mode of nutrition but also in how they reproduce, specialize, and organize into complex structures.
Cell Division
Though both plant and animal cells divide by mitosis (for non-gametic cells) and meiosis (for gametic cells), they differ in the specifics of this process. Unlike animal cells, plant cells lack centrosomes — an organelle responsible for organizing the spindle fibers and segregating the chromosomes during...
Cell Division
Though both plant and animal cells divide by mitosis (for non-gametic cells) and meiosis (for gametic cells), they differ in the specifics of this process. Unlike animal cells, plant cells lack centrosomes — an organelle responsible for organizing the spindle fibers and segregating the chromosomes during...
48.0K
Assembly of Complex Microtubule Structures
2.5K
Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
2.5K
Protein Complex Assembly
16.7K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.7K
Protein Complexes with Interchangeable Parts
2.9K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K
Types of Toxins
3.6K
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
3.6K


