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

La guanosina trifosfato, GTP, un parente stretto dell'ATP, è una piccola molecola importante per la regolazione della funzione proteica. Le G proteins sono proteine regolate dal legame GTP. Queste proteine hanno un'attività intrinseca di GTPasi, cioè, quando GTP è legato, possono catalizzare la sua idrolisi a guanosina difosfato, PIL.Le proteine G sono suddivise in due categorie, piccole e grandi:le G proteins piccole, o monomeriche, sono una singola subunità proteica che è attivata da vari canali di segnalazione intracellulare. Al contrario, le G proteins grandi, o eterotrimeriche, contengono tre subunità, e sono attivate da recettori accoppiati alle G proteins legati alla membrana. Le GTPasi agiscono come un interruttore molecolare, dove lo stato legato al PIL è solitamente inattivo, mentre lo stato legato al GTP è attivo.Il legame GTP, seguito da GTP all'idrolisi del PIL, fa parte del ciclo GTP del PIL. Il ciclo inizia quando un fattore di scambio di guanina, o un GEF, induce un cambiamento conformazionale nella G protein che causa il rilascio del PIL. Il GTP si lega rapidamente al sito nucleotidico, poiché il GTP è abbondante nel citoplasma.La G protein viene ora commutata nel suo stato attivo, con il legame GTP. Le G protein hanno attività GTPasi intrinseca per idrolizzare la molecola legata. Tuttavia, la rottura di GTP da parte dell'enzima è un processo lento, senza segnali cellulari aggiuntivi, pertanto, quando è il momento che la G protein venga disattivata, una proteina attivante la GTPasi, o GAP, si legherà e potenzierà l'attività della GTPasi della proteina.Il GTP è suddiviso in GDP e fosfato inorganico, e la proteina G ritorna al suo stato inattivo, completando il ciclo.

<ol>
	<li>Mishra, A. K., & Lambright, D. G. (2016). Recensione su invito: Piccole GTPasi e i loro GAP. Biopolimeri, 105(8), 431–448.</li>
	<li>Toma-Fukai, S., & Shimizu, T. (2019). Approfondimenti strutturali sul meccanismo di regolazione delle piccole GTPasi da parte dei GEF. Molecole (Basilea, Svizzera), 24(18), 3308.</li>
</ol>

gtpasi e loro regolamentazione

Le proteine leganti i nucleotidi della guanina (proteine G), note anche come GTPasi, sono una super-famiglia di proteine che regolano molti processi cellulari, come la segnalazione cellulare, il trasporto vescicolare e la regolazione della forma e della motilità cellulare. La mutazione o la disfunzione di queste proteine può portare alla malattia. Esistono circa 40.000 proteine G conosciute che possono essere classificate in due gruppi: piccole proteine G, costituite da un singolo dominio, e grandi proteine G, costituite da un multidominio.

Le grandi proteine G, note anche come proteine G eterotrimeriche, sono costituite da tre subunità: α, β e γ. La subunità α ha un dominio conservato che interagisce con i recettori accoppiati alle proteine G per mediare la segnalazione transmembrana.

Le piccole proteine G sono una singola subunità e segnalano in tutta la cellula in una varietà di percorsi. Sono divise in cinque sottofamiglie in base alla sequenza e alla funzione: Ras, Rho, Rab, Ran e Arf. Le mutazioni nella sottofamiglia Ras portano alla formazione di tumori cancerosi nei polmoni, nel colon e nel pancreas. La sottofamiglia Rho regola la riorganizzazione dell'actina e la dinamica del citoscheletro dei microtubuli. La sottofamiglia Rab, la più grande famiglia di piccole proteine G, regola il trasporto delle vescicole e il traffico di membrana nelle vie secretorie ed endocitiche. La sottofamiglia Ran regola il trasporto nucleocitoplasmatico di RNA e proteine attraverso l'assemblaggio e la funzione del poro nucleare e del fuso mitotico. La sottofamiglia Arf è coinvolta nel trasporto delle vescicole e nel traffico di membrana.

Le proteine G sono regolate dal legame GTP/GDP e hanno attività GTPasi intrinseca, il che significa che possono idrolizzare GTP in GDP. Quando il GTP è legato, la proteina G è nello stato “ON”, cioè la proteina promuoverà cascate di segnalazione nella cellula. Quando il GDP è vincolato,  nello stato “OFF”, causerà l’interruzione della segnalazione. La regolazione dell'attivazione della proteina G ulteriormente controllata dai fattori di scambio dei nucleotidi della guanina (GEF), che aiutano nella dissociazione del GDP, e dalle proteine che attivano la GTPasi (GAP) che stimolano l'idrolisi del GTP. Inoltre, gli inibitori della dissociazione della guanina (GDI) possono legarsi a piccole GTPasi e regolare la loro posizione nella membrana o nel citoplasma.

GTPasi e loro regolamentazione

Le proteine leganti i nucleotidi della guanina (proteine G), note anche come GTPasi, sono una superfamiglia di proteine che regolano molti processi cellulari, come ...

Education

Didattica

JoVE Core

Cell Biology

Biologia cellulare

Unit 1

Unità 1

Protein Function

Funzione proteica

KEY TERMS AND CONCEPTS

TERMINI E CONCETTI CHIAVE

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

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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

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protein kinases and phosphatases

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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

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protein complexes with interchangeable parts

protein-complexes-with-interchangeable-parts

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mechanical protein function

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structural protein function

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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

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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

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HS-LS1-3

GTPase Molecular Switches and Control

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