電圧とcAMPによってゲートされた精子特異の溶媒の構造
Valeria Kalienkova1,2, Martin F Peter1,3, Jan Rheinberger3
1Groningen Biomolecular Sciences and Biotechnology, University of Groningen, Groningen, The Netherlands.
Nature
|October 25, 2023
まとめ
この研究は,精子特異のナトリウム-水素交換器 (SLC9C1) の構造を明らかにし,キメラのトランスポーターは男性の生育に不可欠です. この発見は オンデマンドの避妊薬の開発に 新たな目標をもたらします
科学分野:
- 生物化学
- 構造生物学
- 分子生理学
背景:
- 精子特異のナトリウム-水素交換体 (SLC9C1) は男性の生育に不可欠です.
- これらのトランスポーターは,溶質キャリアとイオンチャネルの特徴を統合したユニークな三部位ドメイン組成を有する.
- そのメカニズムは 電圧感知と周期的な核酸調節です
研究 の 目的:
- ゲート構造とゲートメカニズムを解明する
- ボルトセンシングとトランスポートドメイン間のアロステリックカップリングを理解する.
- トランスポーター活動を調節するサイクルAMPの役割を探求する.
主な方法:
- 異なるリガンド結合状態におけるSpSLC9C1の構造を決定するために,X線結晶学を用いた.
- 構造分析は,ドメインの配置とドメイン間のカップリング要素に焦点を当てた.
- 構造データとアロステリック原理に基づいてゲーティングモデルが提案されました.
主要な成果:
- この研究では,SpSLC9C1のドメインアーキテクチャを明らかにし,新しい構造的結合要素を特定しました.
- 結合ヘリクを通して伝達されるアロステリック効果を含む,電圧依存ゲートのためのメカニズムが提案されています.
- サイクルAMPはダイマーインターフェースを妨害し,電圧センサーの動きを容易にします.
結論:
- SpSLC9C1の構造は,電圧で活性化された二次活性トランスポーターとしてのユニークなメカニズムを洞察します.
- ゲートメカニズムとリガンドの調節を理解することは,男性の生育におけるその機能の鍵です.
- 特徴づけられた構造は,新しい男性避妊薬の開発の潜在的なターゲットです.
関連する概念動画
Voltage-gated Ion Channels
8.3K
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
8.3K
The Significance of Membrane Transport
27.4K
The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
27.4K
Facilitated Transport
12.2K
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...
12.2K
Overview of Secretory Vesicles
8.6K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.6K
Clathrin Coated Vesicles
7.0K
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
7.0K
Primary Active Transport
10.3K
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 embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they would...
10.3K


