Name: gtpase molecular switches and control
Uploaded: 2023-04-30T18:28:43.000Z
Duration: 2 min 14 s
Channel: JoVE

K12 Standards

Next Generation Science Standards

High School

Life Science

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

HS-LS1-1

GTPases and their Regulation

グアノシン三リン酸(GTP)は、ATPの近縁種であり、タンパク質機能の調節に重要な小分子です。 
Gタンパク質は、GTP結合によって制御されるタンパク質です。これらのタンパク質は、GTPが結合すると、その加水分解をグアノシン二リン酸、GDPに触媒することができる固有のGTPアーゼ活性を有する。 
Gタンパク質は、小さいものと大きいものの2つのカテゴリに分けられます。小さな、または単量体のGタンパク質は、さまざまな細胞内シグナル伝達経路によって活性化される単一のタンパク質サブユニットです。
対照的に、大きな、またはヘテロ三量体のGタンパク質は、3つのサブユニットを含み、膜結合Gタンパク質共役受容体によって活性化されます。 
GTPアーゼは分子スイッチとして機能し、通常、GDP結合状態は不活性であり、GTP結合状態は活性です。GTP結合とそれに続くGTPからGDPへの加水分解は、GDP/GTPサイクルの一部です。
このサイクルは、グアニン交換因子であるGEFがGタンパク質のコンフォメーション変化を誘発し、GDPの放出を引き起こすときに始まります。 
GTPは細胞質に豊富に存在するため、GTPは空になったヌクレオチド結合部位に迅速に結合します。Gタンパク質は、GTPが結合した活性状態に切り替わります。 
Gタンパク質は、結合した分子を加水分解する固有のGTPアーゼ活性を持っていますが、酵素によるGTPの分解は、追加の細胞シグナルを伴わないゆっくりとしたプロセスです。
したがって、Gタンパク質のスイッチがオフになると、GTPase活性化タンパク質(GAP)が結合し、タンパク質のGTPase活性を高めます。GTPはGDPと無機リン酸塩に分解され、Gタンパク質は不活性状態に戻り、サイクルが完了します。

<ol>
	<li>ミシュラ、AK、およびランブライト、DG(2016)。招待レビュー: Small GTPase and their GAPs.バイオポリマー, 105(8), 431–448.</li>
	<li>Toma-Fukai, S., & Shimizu, T. (2019).GEFによる低分子GTPaseの制御機構に関する構造的洞察。分子(バーゼル、スイス)、24(18)、3308。</li>
</ol>

gtpアーゼとその規制

GTP アーゼとしても知られるグアニンヌクレオチド結合タンパク質 (G タンパク質) は、細胞シグナル伝達、小胞輸送、細胞の形態と運動性の制御など、多くの細胞プロセスを制御するタンパク質のスーパーファミリーです。 これらのタンパク質の変異や機能不全は疾患を引き起こす可能性があります。既知の G タンパク質は約 40,000 種類あり、単一ドメインからなる小型Gタンパク質と大きなマルチドメイン G タンパク質の2つのグループに大別できます。

ヘテロ三量体 G タンパク質としても知られる大型 G タンパク質は、α、β、γ の 3 つのサブユニットで構成されます。α サブユニットには、G タンパク質共役受容体と相互作用して膜貫通シグナル伝達を媒介する保存されたドメインがあります。

低分子 G タンパク質は単一のサブユニットであり、さまざまな経路で細胞全体にシグナルを送ります。これらは配列と機能に基づいて、Ras、Rho、Rab、Ran、Arf の 5 つのサブファミリーに分類されます。Ras サブファミリーの変異は、肺、結腸、膵臓での癌性腫瘍の形成を引き起こします。Rho サブファミリーは、アクチンの再編成と微小管細胞骨格の動態を制御します。 小型 G タンパク質の中で最大の Rab サブファミリーは、分泌経路およびエンドサイトーシス経路における小胞輸送および膜輸送を制御します。Ran サブファミリーは、核孔および有糸分裂紡錘体の集合および機能を介して、RNA およびタンパク質の核細胞質輸送を調節します。 Arfサブファミリーは小胞輸送と膜輸送に関与しています。

G タンパク質は GTP/GDP 結合によって調節され、固有の GTP アーゼ活性を持っています。つまり、G タンパク質は GTP を GDP に加水分解できます。GTP が結合すると、G タンパク質は「オン」状態になります。つまり、タンパク質は細胞内のシグナル伝達カスケードを促進します。 GDP が結びつけられている場合、GDP は「オフ」状態になり、シグナリングが停止します。G タンパク質活性化の制御は、GDPの解離を助けるグアニンヌクレオチド交換因子(GEF)と、GTP 加水分解を刺激する GTP アーゼ活性化タンパク質(GAP)によってさらに制御されます。さらに、グアニン解離阻害剤(GDI)は低分子 GTP アーゼに結合し、膜または細胞質内での位置を制御します。

GTPアーゼとその規制

グアニンヌクレオチド結合タンパク質(Gタンパク質)は、GTPアーゼとも呼ばれ、細胞などの多くの細胞プロセスを調節するタンパク質のスーパーファミリーです...

Education

JoVE Core

Cell Biology

細胞生物学

Unit 1

ユニット1

Protein Function

タンパク質の機能

KEY TERMS AND CONCEPTS

主要用語と概念

gtpase molecular switches and control

GTPases are molecular switches that help control cell activity. They bind guanosine triphosphate, or GTP, and can change between active and inactive states. This switch-like behavior makes them important in many cell processes.

The protein is active when GTP is bound and inactive when guanosine diphosphate, or GDP, is bound. GTPases can also turn themselves off by breaking down GTP into GDP. This built-in control helps cells regulate when the protein is on or off.

Their activity is regulated by other proteins as well. Some proteins help GTPases exchange GDP for GTP, while others speed up GTP breakdown. These regulators make sure GTPases respond at the right time and in the right place.

GTPase Molecular Switches and Control

ligand binding sites

Ligand Binding Sites in Proteins

Ligand binding sites are specific parts of a protein where a ligand can attach. A ligand is a molecule that binds to another molecule, often to help start or change a biological process. These sites matter because the shape and chemistry of the protein help determine which ligands can fit and bind. Proteins do not bind every ligand in the same way. The binding site provides a matching surface that supports a close interaction. In many cases, this interaction is important for how cells respond...

protein-protein interfaces

Protein Binding Surfaces and Contacts

Protein binding surfaces and contacts help proteins recognize and attach to each other. These interfaces are the regions where two proteins meet and interact. They are important for many cell processes and for how proteins work together. A protein-protein interface is not just a random touch point. It is shaped by the three-dimensional form of each protein. The matching surfaces allow a stable interaction to form when the proteins fit together well. Studying these interfaces helps explain how...

conserved binding sites

Conserved Binding Sites in Protein Families

Conserved binding sites are regions on proteins that stay similar across related proteins. These shared areas often help proteins interact with the same molecules. For this reason, they are useful clues when comparing protein families. A conserved site can help identify where a protein binds. It can also show which parts of the protein are important for function. When the same pattern appears in several proteins, it suggests that the site has been kept through evolution. Scientists look at...

cofactors and coenzymes

Enzyme Helpers: Metals and Vitamins

Enzyme helpers include cofactors and coenzymes. Enzymes are proteins made of amino acids, and the functional groups on those amino acids can drive many chemical reactions through ionic interactions or acid-base reactions. But amino acids alone cannot handle oxidation-reduction and group transfer reactions, so they need non-protein helpers called cofactors. Cofactors are often described as the chemical teeth of an enzyme. They can be metal ions or organic molecules called coenzymes. These...

cooperative allosteric transitions

Allosteric Changes in Protein Shape

Allosteric changes in protein shape help explain how some proteins switch between active and inactive states. These transitions are cooperative, which means a change in one part of the protein can affect other parts of the same molecule. The video focuses on how these shifts in shape support protein function. It also shows that allosteric transitions can be described with different models. In the concerted model, the protein changes shape as a whole. In the sequential model, the change happens...

protein kinases and phosphatases

Protein Kinases and Phosphatases in Cell Control

Protein kinases and phosphatases help control how proteins work in cells. Kinases add phosphate groups to proteins. Phosphatases remove those phosphate groups. This phosphorylation and dephosphorylation process can change a protein’s shape and activity. It is one way cells turn protein function on or off at the right time. These changes also help cells respond to signals and manage many cell activities. Together, protein kinases and phosphatases keep cellular signaling balanced. When one adds...

gtpases and their regulation

GTPases are molecular switches that help control cell activity. They bind guanosine triphosphate, or GTP, and can change between active and inactive states. This switch-like behavior makes them important in many cell processes. The protein is active when GTP is bound and inactive when guanosine diphosphate, or GDP, is bound. GTPases can also turn themselves off by breaking down GTP into GDP. This built-in control helps cells regulate when the protein is on or off. Their activity is regulated...

covalently linked protein regulators

Protein Regulation by Covalent Bonds

Protein regulation by covalent bonds helps control how cells respond to changing conditions. A covalent bond is a strong chemical link, and in this context it can change how a protein behaves. Some regulators work by attaching a chemical group directly to a protein. This covalent change can alter the protein's activity, its location in the cell, or how long it stays active. Because the change is built into the protein itself, it can have a strong effect on cell function. Covalently linked...

protein complexes with interchangeable parts

protein-complexes-with-interchangeable-parts

Modular Protein Complexes in Cells

Protein complexes in cells can be built from interchangeable parts. This modular design lets some complexes share common subunits while still changing their behavior. A well-known example is the ubiquitin ligase complex called SCF. SCF stands for Skp1-Cullin-F-box, and it helps attach ubiquitin, a small protein tag, to target proteins. The core of SCF stays the same, but the F-box protein can change. The interchangeable F-box subunit gives the complex its specificity. Different F-box proteins...

mechanical protein function

Proteins That Generate Cell Movement

Mechanical proteins help cells and tissues move. They turn chemical energy into force and motion. This process is important in many biological systems. These proteins are also called motor proteins. They interact with cell structures and can produce directed movement. In muscle cells, they support contraction. In other cells, they help with transport and shape changes. Mechanical protein function is a key part of how living systems work. It links protein activity to movement at the cellular...

structural protein function

Structural Proteins in Cells and Tissues

Structural proteins help cells and tissues keep their shape and strength. They are an important part of living systems because they provide support where it is needed most. Many structural proteins form fibers or other sturdy forms that resist stretching and wear. These proteins work as building materials in the body and help keep structures stable over time. Examples of structural proteins include collagen, actin, myosin, and keratin. Each one supports a different part of the body, but all...

protein networks

Mapping Protein Interaction Networks

Protein interaction networks show how proteins work together inside a cell. These networks help scientists see which proteins connect with each other and how those links support cell activity. Researchers often use online tools to build and study these networks. The transcript points to IntAct and STRING as examples of resources that can help predict and organize protein interactions. These tools make it easier to compare protein links and look for patterns in the network. Protein networks...

key terms and concepts

Explore how GTPases act as molecular switches and how GTP and GDP binding, plus regulator proteins, control when they are active or inactive.

GTPase Molecular Switches and Control | JoVE K12

cell biology

JoVE Core 細胞生物学は、複雑な細胞プロセスを、わかりやすく包括的なアニメーション ビデオ レッスンで説明します。このコレクションは、細胞小器官や膜、細胞輸送、細胞のエネルギー学など、細胞の必須コンポーネントと機能に焦点を当てています。これは、実際の研究実験における細胞生物学の応用を実証する科学者による実際のビデオによって補足されています。

Characteristics of Life

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Protein Complex Assembly

Protein and Protein Structures

Conjugated Proteins

Proteins: From Genes to Degradation

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Protein Organization

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Protein-Protein Interfaces

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Covalently Linked Protein Regulators

Protein Complexes with Interchangeable Parts

Mechanical Protein Function

Structural Protein Function

Protein Networks

Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins, which carry out the essential functions of life through systems of specialized cells. [Assessment Boundary: Assessment does not include identification of specific cell or tissue types, whole body systems, specific protein structures and functions, or the biochemistry of protein synthesis.]

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The Sympathetic Nervous System

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Develop and use a model to illustrate the hierarchical organization of interacting systems that provide specific functions within multicellular organisms. [Clarification Statement: Emphasis is on functions at the organism system level such as nutrient uptake, water delivery, and organism movement in response to neural stimuli. An example of an interacting system could be an artery depending on the proper function of elastic tissue and smooth muscle to regulate and deliver the proper amount of blood within the circulatory system.] [Assessment Boundary: Assessment does not include interactions and functions at the molecular or chemical reaction level.]

HS-LS1-2

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HS-LS1-3

GTPase Molecular Switches and Control

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