カルシウム活性化された非選択的カチオンチャンネルTRPM4の構造

Jiangtao Guo^1,2, Ji She^1,2, Weizhong Zeng^1,2,3

¹Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA.

Nature

|December 7, 2017

まとめ

この研究は,カルシウム活性化イオンチャネルであるTRPM4の分子構造を明らかにした. これらの構造は,ATPがTRPM4の活動を抑制し,単価イオンをどのように選択するかを示しています.

科学分野:

生物化学
構造生物学
分子生理学

背景:

トランジエントレセプターポテンシャルメラスタチン4 (TRPM4) チャンネルは,カルシウムで活性化され,非選択的なカチオンチャンネルです.
TRPM4の活性は,フォスファディチルイノシトール-4,5-ビスホスファート (PtdIns(4,5) P2によって調節される.
TRPM4の構造を理解することは,ゲートメカニズムと生理学的役割の解明に不可欠です.

研究の目的:

マウスTRPM4チャネルの高解像度構造を決定する.
ATP阻害と単価イオン選択性の構造的基礎を調査する.
TRPMチャネルファミリーの全体的なアーキテクチャを洞察する.

主な方法:

電子冷凍顕微鏡 (冷凍EM)
ATPの存在と欠如におけるTRPM4の構造分析

主要な成果:

この研究は,マウスTRPM4の冷凍-EM構造を提示し,三層構造を明らかにしています.
ATPはN端核酸結合領域に結合し,チャネル活動を阻害する.
Gln973が決定的な広い選択性フィルターは,単価イオン透過性を確保します.
S1-S4とS6後のTRPドメインはゲート装置を形成し,Ca2+とPtdInsを結合する可能性がある.

結論:

決定された構造は,TRPM4の分子構造の基本的な理解を提供します.
これらの発見は,TRPM4の複雑なゲートメカニズムを解読するために不可欠です.
この研究は,ATPと脂質によるTRPM4のイオン選択性と調節の構造的基礎を提供する.

さらに関連する動画

08:27

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

10.0K

07:17

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels

Published on: December 13, 2024

1.9K

関連する概念動画

01:12

Mechanically-gated Ion Channels

7.9K

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...

7.9K

01:16

Calmodulin-dependent Signaling

6.6K

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...

6.6K

01:43

Thermosensation

34.0K

Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...

34.0K

01:26

Voltage-gated Ion Channels

11.1K

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 types of...

11.1K

01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

4.2K

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...

4.2K

01:19

Ligand-gated Ion Channels

14.5K

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...