Arrestin

Function

Arrestin (ARR) is a ubiquitous protein which binds to the G protein-coupled receptor after its phosphorylation. ARR binding blocks further G protein-mediated signaling and redirects signaling to alternative non-G protein-independent pathways. Hence, ARR are versatile adaptor molecules which can also activate signaling cascades and are involved in nuclear functions.^[1]

Arrestin-2 is regulator of B-cell function^[2].
Arrestin-3 assists in activation of JNK3 ^[3].
Arrestin-4 or cone arrestin binds in a cone cell th G protein kinase to desensitise opsin.
S-arrestin binds to photo activated Rho and terminates its signaling.

Structural highlights

ARR consist of 2 domains. The N terminal domain structure is immunoglobulin-like. The binding site of phosphorylated light-activated rhodopsin is located at the N terminal of ARR.

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3D Structures of arrestin

Arrestin 3D structures

ReferencesReferences

↑ Hirsch JA, Schubert C, Gurevich VV, Sigler PB. The 2.8 A crystal structure of visual arrestin: a model for arrestin's regulation. Cell. 1999 Apr 16;97(2):257-69. PMID:10219246
↑ Zhu L, Almaça J, Dadi PK, Hong H, Sakamoto W, Rossi M, Lee RJ, Vierra NC, Lu H, Cui Y, McMillin SM, Perry NA, Gurevich VV, Lee A, Kuo B, Leapman RD, Matschinsky FM, Doliba NM, Urs NM, Caron MG, Jacobson DA, Caicedo A, Wess J. β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions. Nat Commun. 2017 Feb 1;8:14295. PMID:28145434 doi:10.1038/ncomms14295
↑ Zheng C, Weinstein LD, Nguyen KK, Grewal A, Gurevich EV, Gurevich VV. GPCR Binding and JNK3 Activation by Arrestin-3 Have Different Structural Requirements. Cells. 2023 Jun 6;12(12):1563. PMID:37371033 doi:10.3390/cells12121563

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Hirsch JA, Schubert C, Gurevich VV, Sigler PB. The 2.8 A crystal structure of visual arrestin: a model for arrestin's regulation. Cell. 1999 Apr 16;97(2):257-69. PMID:10219246

[2] Zhu L, Almaça J, Dadi PK, Hong H, Sakamoto W, Rossi M, Lee RJ, Vierra NC, Lu H, Cui Y, McMillin SM, Perry NA, Gurevich VV, Lee A, Kuo B, Leapman RD, Matschinsky FM, Doliba NM, Urs NM, Caron MG, Jacobson DA, Caicedo A, Wess J. β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions. Nat Commun. 2017 Feb 1;8:14295. PMID:28145434 doi:10.1038/ncomms14295

[3] Zheng C, Weinstein LD, Nguyen KK, Grewal A, Gurevich EV, Gurevich VV. GPCR Binding and JNK3 Activation by Arrestin-3 Have Different Structural Requirements. Cells. 2023 Jun 6;12(12):1563. PMID:37371033 doi:10.3390/cells12121563

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