Structural Evidence for Visual Arrestin Priming Via Complexation of Phosphoinositols
Overview
Biotechnology
Cell Biology
Molecular Biology
Authors
Affiliations
Visual arrestin (Arr1) terminates rhodopsin signaling by blocking its interaction with transducin. To do this, Arr1 translocates from the inner to the outer segment of photoreceptors upon light stimulation. Mounting evidence indicates that inositol phosphates (InsPs) affect Arr1 activity, but the Arr1-InsP molecular interaction remains poorly defined. We report the structure of bovine Arr1 in a ligand-free state featuring a near-complete model of the previously unresolved C-tail, which plays a crucial role in regulating Arr1 activity. InsPs bind to the N-domain basic patch thus displacing the C-tail, suggesting that they prime Arr1 for interaction with rhodopsin and help direct Arr1 translocation. These structures exhibit intact polar cores, suggesting that C-tail removal by InsP binding is insufficient to activate Arr1. These results show how Arr1 activity can be controlled by endogenous InsPs in molecular detail.
The Role of Individual Residues in the N-Terminus of Arrestin-1 in Rhodopsin Binding.
Vishnivetskiy S, Paul T, Gurevich E, Gurevich V Int J Mol Sci. 2025; 26(2).
PMID: 39859432 PMC: 11765510. DOI: 10.3390/ijms26020715.
Insights into the Activation and Self-Association of Arrestin-1.
Salom D, Kiser P, Palczewski K Biochemistry. 2024; 64(2):364-376.
PMID: 39704710 PMC: 11784764. DOI: 10.1021/acs.biochem.4c00632.
Arrestins: A Small Family of Multi-Functional Proteins.
Gurevich V Int J Mol Sci. 2024; 25(11).
PMID: 38892473 PMC: 11173308. DOI: 10.3390/ijms25116284.
Expression of Untagged Arrestins in E. coli and Their Purification.
Vishnivetskiy S, Zhan X, Gurevich V Curr Protoc. 2023; 3(9):e832.
PMID: 37671938 PMC: 10491425. DOI: 10.1002/cpz1.832.
GPCR Binding and JNK3 Activation by Arrestin-3 Have Different Structural Requirements.
Zheng C, Weinstein L, Nguyen K, Grewal A, Gurevich E, Gurevich V Cells. 2023; 12(12).
PMID: 37371033 PMC: 10296906. DOI: 10.3390/cells12121563.