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

Guanosintriphosphat, GTP, ein naher Verwandter von ATP, ist ein kleines Molekül, das für die Regulation der Proteinfunktion wichtig ist. 
G-Proteine sind Proteine, die durch GTP-Bindung reguliert werden. Diese Proteine haben eine intrinsische GTPase-Aktivität, d.h. wenn GTP gebunden ist, können sie seine Hydrolyse zu Guanosindiphosphat, GDP, katalysieren. 
G-Proteine werden in zwei Kategorien eingeteilt, klein und groß. Die kleinen oder monomeren G-Proteine sind eine einzelne Proteinuntereinheit, die durch verschiedene intrazelluläre Signalwege aktiviert wird.
Im Gegensatz dazu enthalten die großen oder heterotrimeren G-Proteine drei Untereinheiten und werden durch membrangebundene G-Protein-gekoppelte Rezeptoren aktiviert. 
GTPasen fungieren als molekularer Schalter, wobei der GDP-gebundene Zustand normalerweise inaktiv ist, während der GTP-gebundene Zustand aktiv ist. Die GTP-Bindung, gefolgt von der GTP-zu-BIP-Hydrolyse, ist Teil des BIP/GTP-Zyklus.
Der Zyklus beginnt, wenn ein Guanin-Austauschfaktor, GEF, eine Konformationsänderung im G-Protein induziert, die die Freisetzung von GDP bewirkt. 
GTP bindet schnell an die nun leere Nukleotid-Bindungsstelle, da GTP im Zytoplasma reichlich vorhanden ist. Das G-Protein wird nun in seinen aktiven Zustand geschaltet, wobei GTP gebunden ist. 
G-Proteine haben eine intrinsische GTPase-Aktivität, um das gebundene Molekül zu hydrolysieren; der GTP-Abbau durch das Enzym ist jedoch ein langsamer Prozess ohne zusätzliche zelluläre Signale.
Wenn es also an der Zeit ist, das G-Protein auszuschalten, bindet ein GTPase-aktivierendes Protein (GAP) und erhöht die GTPase-Aktivität des Proteins. Das GTP wird in GDP und anorganisches Phosphat zerlegt, und das G-Protein kehrt in seinen inaktiven Zustand zurück, wodurch der Zyklus abgeschlossen ist.

<ol>
	<li>Mishra, A. K., & Lambright, D. G. (2016). Eingeladene Überprüfung: Kleine GTPasen und ihre GAPs. Biopolymere, 105(8), 431–448.</li>
	<li>Toma-Fukai, S., & Shimizu, T. (2019). Strukturelle Einblicke in den Regulationsmechanismus kleiner GTPasen durch GEFs. Moleküle (Basel, Schweiz), 24(18), 3308.</li>
</ol>

gtpasen und ihre regulierung

Guaninnukleotid-bindende Proteine (G-Proteine), auch bekannt als GTPasen, sind eine Superfamilie von Proteinen, die viele zelluläre Prozesse wie Zellsignalübertragung, vesikulären Transport und die Regulierung von Zellform und -beweglichkeit steuern. Mutationen oder Dysfunktionen dieser Proteine können zu Krankheiten führen. Es sind etwa 40.000 bekannte G-Proteine vorhanden, die grob in zwei Gruppen eingeteilt werden können: kleine G-Proteine, die aus einer einzigen Domäne bestehen, und große multidomänige G-Proteine.

Große G-Proteine, auch bekannt als heterotrimere G-Proteine, bestehen aus drei Untereinheiten — α, β und γ. Die α-Untereinheit besitzt eine konservierte Domäne, die mit G-Protein-gekoppelten Rezeptoren interagiert, um transmembrane Signalübertragung zu vermitteln.

Kleine G-Proteine bestehen aus einer einzigen Untereinheit und signalisieren in der Zelle über eine Vielzahl von Wegen. Sie werden basierend auf Sequenz und Funktion in fünf Unterfamilien unterteilt: Ras, Rho, Rab, Ran und Arf. Mutationen in der Ras-Unterfamilie führen zur Bildung von Krebstumoren in Lunge, Dickdarm und Bauchspeicheldrüse. Die Rho-Unterfamilie reguliert die Reorganisation von Aktin und die Dynamik des Mikrotubuli-Zytoskeletts. Die Rab-Unterfamilie, die größte kleine G-Protein-Familie, reguliert den Vesikeltransport und den Membranverkehr in sekretorischen und endozytotischen Wegen. Die Ran-Unterfamilie reguliert den nukleozytoplasmatischen Transport von RNA und Proteinen durch die Kernpore sowie die Montage und Funktion des Mitose-Spindelapparats. Die Arf-Unterfamilie ist an Vesikeltransport und Membranverkehr beteiligt.

G-Proteine werden durch GTP/GDP-Bindung reguliert und besitzen eine intrinsische GTPase-Aktivität, was bedeutet, dass sie GTP zu GDP hydrolysieren können. Wenn GTP gebunden ist, befindet sich das G-Protein im „ON“-Zustand, d.h., das Protein fördert Signalkaskaden in der Zelle. Wenn GDP gebunden ist, befindet es sich im „OFF“-Zustand, was dazu führt, dass die Signalgebung stoppt. Die Regulation der G-Protein-Aktivierung wird weiterhin durch Guaninnukleotid-Austauschfaktoren (GEFs) reguliert, die bei der GDP-Dissoziation helfen, und GTPase-aktivierende Proteine (GAPs), die die GTP-Hydrolyse stimulieren. Darüber hinaus können Guaninnukleotid-Dissoziationsinhibitoren (GDIs) an kleine GTPasen binden und deren Position in der Membran oder im Zytoplasma regulieren.

GTPasen und ihre Regulierung

Guanin-Nukleotid-bindende Proteine (G-Proteine), auch bekannt als GTPasen, sind eine Superfamilie von Proteinen, die viele zelluläre Prozesse regulieren, wie z. B. ...

Education

Lehre

JoVE Core

Cell Biology

Zellbiologie

Unit 1

Einheit 1

Protein Function

Proteinfunktion

KEY TERMS AND CONCEPTS

KERNBEGRIFFE UND KONZEPTE

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

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protein-protein interfaces

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conserved binding sites

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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

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mechanical protein function

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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...

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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 Zellbiologie veranschaulicht komplexe zelluläre Prozesse in leicht verständlichen und dennoch umfassenden animierten Videolektionen. Diese Sammlung konzentriert sich auf die wesentlichen Bestandteile und Funktionen von Zellen, einschließlich Organellen und Membranen, Zelltransport und Zellenergie. Ergänzt wird sie durch Videos von Wissenschaftlern in Aktion, die die Anwendung der Zellbiologie in realen Forschungsexperimenten demonstrieren.

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HS-LS1-2

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HS-LS1-3

GTPase Molecular Switches and Control

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