Arrestin: Difference between revisions
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== Arrestin == | |||
[[File:1CF1.png|Arrestin|thumb|right]] | |||
==Structure== | '''Arrestin''' is a family of proteins that play a crucial role in the regulation of [[G protein-coupled receptors]] (GPCRs). These proteins are involved in the desensitization of GPCRs, which are a large family of receptors that respond to a variety of external signals. Arrestins are responsible for terminating the signaling of GPCRs and facilitating their internalization. | ||
Arrestins are composed of two main domains | |||
== Structure == | |||
Arrestins are composed of two main domains, the N-domain and the C-domain, which are connected by a flexible hinge region. This structure allows arrestins to undergo conformational changes necessary for their function. The crystal structures of arrestins, such as those from the [[Protein Data Bank]] entries 1CF1 and 1G4M, have provided insights into their molecular architecture. | |||
[[File:PDB_1cf1_EBI.jpg|Arrestin structure from PDB 1CF1|thumb|left]] | |||
== Function == | |||
Arrestins are primarily known for their role in the desensitization of GPCRs. When a GPCR is activated by a ligand, it undergoes phosphorylation by [[G protein-coupled receptor kinases]] (GRKs). This phosphorylation creates a binding site for arrestins, which then bind to the receptor, preventing further G protein activation. This process effectively "arrests" the receptor, hence the name. | |||
In addition to desensitization, arrestins also facilitate the internalization of GPCRs through clathrin-mediated endocytosis. Once internalized, receptors can be either recycled back to the cell surface or targeted for degradation. | |||
== Types of Arrestins == | |||
There are four known types of arrestins in mammals: | There are four known types of arrestins in mammals: | ||
* '''Visual arrestins''': These include arrestin-1 and arrestin-4, which are primarily found in the [[retina]] and are involved in the desensitization of [[rhodopsin]] | * '''Visual arrestins''': These include arrestin-1 and arrestin-4, which are primarily found in the [[retina]] and are involved in the desensitization of [[rhodopsin]]. | ||
* '''Non-visual arrestins''': Arrestin-2 and arrestin-3, also known as | * '''Non-visual arrestins''': Arrestin-2 and arrestin-3, also known as β-arrestin-1 and β-arrestin-2, are ubiquitously expressed and regulate a wide range of GPCRs throughout the body. | ||
== Role in Signaling Pathways == | |||
Beyond their role in desensitization, arrestins are also involved in signaling pathways independent of G proteins. They can act as scaffolds for various signaling molecules, thereby influencing pathways such as the [[MAPK/ERK pathway]], which is important for cell growth and differentiation. | |||
[[File:PDB_1g4m_EBI.jpg|Arrestin structure from PDB 1G4M|thumb|right]] | |||
== Clinical Significance == | |||
Dysregulation of arrestin function has been implicated in various diseases. For example, mutations in visual arrestins can lead to retinal degenerative diseases. Additionally, the modulation of arrestin pathways is being explored as a therapeutic strategy for conditions such as heart failure and cancer. | |||
Dysregulation of arrestin function has been implicated in various diseases. For example, mutations in visual arrestins can lead to retinal degenerative diseases, | |||
== | == Related Pages == | ||
* [[G protein-coupled receptor]] | * [[G protein-coupled receptor]] | ||
* [[Rhodopsin]] | * [[Rhodopsin]] | ||
* [[ | * [[G protein-coupled receptor kinase]] | ||
* [[MAPK/ERK pathway]] | |||
{{Protein-stub}} | |||
[[Category:Signal transduction]] | [[Category:Signal transduction]] | ||
[[Category:Proteins]] | [[Category:Proteins]] | ||
[[Category:Cell signaling]] | |||
Latest revision as of 18:49, 23 March 2025
Arrestin[edit]
Arrestin is a family of proteins that play a crucial role in the regulation of G protein-coupled receptors (GPCRs). These proteins are involved in the desensitization of GPCRs, which are a large family of receptors that respond to a variety of external signals. Arrestins are responsible for terminating the signaling of GPCRs and facilitating their internalization.
Structure[edit]
Arrestins are composed of two main domains, the N-domain and the C-domain, which are connected by a flexible hinge region. This structure allows arrestins to undergo conformational changes necessary for their function. The crystal structures of arrestins, such as those from the Protein Data Bank entries 1CF1 and 1G4M, have provided insights into their molecular architecture.
Function[edit]
Arrestins are primarily known for their role in the desensitization of GPCRs. When a GPCR is activated by a ligand, it undergoes phosphorylation by G protein-coupled receptor kinases (GRKs). This phosphorylation creates a binding site for arrestins, which then bind to the receptor, preventing further G protein activation. This process effectively "arrests" the receptor, hence the name.
In addition to desensitization, arrestins also facilitate the internalization of GPCRs through clathrin-mediated endocytosis. Once internalized, receptors can be either recycled back to the cell surface or targeted for degradation.
Types of Arrestins[edit]
There are four known types of arrestins in mammals:
- Visual arrestins: These include arrestin-1 and arrestin-4, which are primarily found in the retina and are involved in the desensitization of rhodopsin.
- Non-visual arrestins: Arrestin-2 and arrestin-3, also known as β-arrestin-1 and β-arrestin-2, are ubiquitously expressed and regulate a wide range of GPCRs throughout the body.
Role in Signaling Pathways[edit]
Beyond their role in desensitization, arrestins are also involved in signaling pathways independent of G proteins. They can act as scaffolds for various signaling molecules, thereby influencing pathways such as the MAPK/ERK pathway, which is important for cell growth and differentiation.
Clinical Significance[edit]
Dysregulation of arrestin function has been implicated in various diseases. For example, mutations in visual arrestins can lead to retinal degenerative diseases. Additionally, the modulation of arrestin pathways is being explored as a therapeutic strategy for conditions such as heart failure and cancer.
Related Pages[edit]
