Name: g protein-coupled receptor signaling
Uploaded: 2023-06-23T15:38:45.000Z
Duration: 1 min 15 s
Channel: JoVE

Os receptores acoplados à proteína G ou GPCRs são receptores de superfície celular que se associam às proteínas G heterotriméricas e medeiam a resposta celular a sinais como luz, hormônios, citocinas e neurotransmissores.
Todos os GPCRs contêm sete alfa-hélices transmembranares separadas por alças citosólicas alternadas que se ligam a uma proteína G e alças extracelulares que se ligam ao ligante.
Na ausência de ligantes, um GPCR é inativo.
A ligação do ligante induz uma mudança conformacional na alça citosólica do GPCR. O GPCR ativado agora pode se ligar à proteína G ligada ao GDP inativo com maior afinidade para formar um complexo de proteína receptor-G.
A interação receptor-proteína G induz ainda mais mudanças conformacionais na proteína G, desencadeando a troca de GDP com GTP.
Em seguida, a subunidade ligada ao GTP da proteína G se dissocia do GPCR e ativa os efetores a jusante para mediar a visão, o olfato, o paladar e a resposta imune.

<ol>
	<li>Yang D, Zhou Q, Labroska V, Qin S, Darbalaei S, Wu Y, Yuliantie E, Xie L, Tao H, Cheng J, Liu Q, Zhao S, Shui W, Jiang Y, Wang MW. Receptores acoplados à proteína G: descoberta de medicamentos baseada em estrutura e função. Alvo de transdução de sinal lá. 8 de janeiro de 2021; 6(1):7. DOI: 10.1038/S41392-020-00435-W.</li>
	<li>Sutkeviciute I, Vilardaga JP. Insights estruturais sobre os modos de sinalização emergentes de receptores acoplados à proteína G. J Biol Chem. 2020 14 de agosto; 295(33):11626-11642. DOI: 10.1074/JBC. REV120.009348.</li>
</ol>

receptores acoplados à proteína g

G Protein-coupled Receptors

Os receptores acoplados à proteína G, ou GPCRs, são receptores ligados à membrana que se associam transitoriamente com proteínas G heterotriméricas e induzem uma resposta apropriada a estímulos sensoriais, como luz, odores, hormônios, citocinas ou neurotransmissores. 

 Os GPCRs também são chamados de receptores heptaélicos, 7TM ou serpentina e consistem em sete hélices alfa transmembrana (H1-H7) que abrangem a bicamada para formar um núcleo cilíndrico. As hélices transmembrana são conectadas por três alças extracelulares e três alças citosólicas. Juntamente com as alças extracelulares, as alfa-hélices transmembrana formam a bolsa central de ligação ao ligante do GPCR. Em contraste, a terceira alça citosólica funciona como sítio de ligação à proteína G heterotrimérica. 

 A ligação do ligante ativa os GPCRs à medida que sofre uma mudança conformacional e também se liga a proteínas G heterotriméricas com alta afinidade. Um GPCR ativado pode ligar e ativar múltiplas proteínas G para amplificar o sinal. As proteínas G, por sua vez, ligam-se e ativam efetores downstream e provocam uma resposta celular. 

 Embora estruturalmente todos os GPCRs de mamíferos consistam em sete domínios alfa-helicoidais transmembranares, eles diferem consideravelmente em sua sequência e funcionalidade. Os GPCRs são amplamente categorizados em cinco classes, incluindo Classe A (semelhante à rodopsina), Classe B (semelhante ao receptor de secretina, ou B1), Classe B2/tipo de adesão, Classe C (semelhante ao receptor de glutamato) e Classe F (semelhante a frizzled). 
 <ul style="padding-left: 35px; list-style-type: disc;"> 
 <li>A Classe A forma a maior subfamília de GPCRs, que inclui rodopsinas e receptores beta-adrenérgicos.</li> 
 <li>A classe B compreende os receptores de ligação hormonal, como glucagon, hormônio da paratireoide e receptores de peptídeo intestinal vasoativo (VIP).
 <ul style="padding-left: 35px; list-style-type: disc;"> 
 <li>A classe de receptores de adesão, ou B2, inclui os receptores acoplados à proteína G de adesão, ou grupos de receptores ADGR, como ADGRL1 e ADGRG1, que são essenciais para a adesão e migração celular.</li>
 </ul> 
 </li> 
 <li>A classe C inclui receptores sensíveis ao cálcio, receptores tipo B do ácido gama-aminobutírico (GABA), receptores metabotrópicos de glutamato e vários receptores gustativos. Ao contrário dos outros, este grupo usa um módulo característico de venus fly trap para ligação do ligante.</li> 
 <li>A classe F, também, chamada de frisado, inclui receptores suavizados, ou Smo, e atua no desenvolvimento embrionário.</li>
 </ul> 

 No geral, os humanos consistem em mais de 800 GPCRs. Muitos deles detectam hormônios, fatores de crescimento ou ligantes endógenos, enquanto vários outros estão envolvidos nas respostas olfativas e gustativas. 

 Assim, os GPCRs regulam vias fisiológicas críticas e são um excelente alvo de medicamentos para o tratamento de doenças como diabetes, câncer, obesidade, depressão ou doença de Alzheimer. Quase 35% dos medicamentos aprovados implementam os seus efeitos terapêuticos interagindo seletivamente com GPCRs específicos. Uma classe de medicamentos comumente usada, os betabloqueadores, têm como alvo os receptores beta-adrenérgicos e tratam doenças como hipertensão, arritmia cardíaca e ansiedade. Os GPCRs fornecem um alvo eficaz para criar um arsenal para uma gama variada de doenças.

Receptores Acoplados à Proteína G

Os Receptores Acoplados à Proteína G ou GPCRs são receptores ligados à membrana que se associam transitoriamente às proteínas G heterotriméricas e induzem um ...

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Anatomy and Physiology

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Essential Cellular Processes

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KEY TERMS AND CONCEPTS

TERMOS-CHAVE E CONCEITOS

g protein-coupled receptor signaling

G protein-coupled receptors are a major class of cell-surface receptors. They help cells detect signals outside the cell and pass that information inward. These receptors are important in many kinds of cell communication.

When a signal binds to a G protein-coupled receptor, the receptor changes shape. That change activates a G protein inside the cell. The activated G protein can then start a signaling pathway.

This signaling system includes the receptor, the G protein, and the downstream response. It allows cells to respond to specific signals in a controlled way. G protein-coupled receptors are studied because they play a central role in how cells react to their environment.

G Protein-coupled Receptor Signaling

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g protein-coupled receptors

G protein-coupled receptors are a major class of cell-surface receptors. They help cells detect signals outside the cell and pass that information inward. These receptors are important in many kinds of cell communication. When a signal binds to a G protein-coupled receptor, the receptor changes shape. That change activates a G protein inside the cell. The activated G protein can then start a signaling pathway. This signaling system includes the receptor, the G protein, and the downstream...

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G Protein-coupled Receptor Signaling | JoVE K12

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G Protein-coupled Receptor Signaling

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