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Arrestins: structural disorder creates rich functionality

-arrestin2 or hTHY-ARRX), and arrestin-4 (cone or X-arrestin). COMPLIANCE WITH ETHICS GUIDELINES Vsevolod V. Gurevich, Eugenia V. Gurevich, and Vladimir N. Uversky declare that they have no conflict of

C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor

Rod photoreceptors generate measurable responses to single-photon activation of individual molecules of the G protein-coupled receptor (GPCR), rhodopsin. Timely rhodopsin desensitization depends on phosphorylation and arrestin binding, which quenches G protein activation. Rhodopsin phosphorylation has been measured biochemically at C-terminal serine residues, suggesting that...

The Origin and Evolution of G Protein-Coupled Receptor Kinases

G protein-coupled receptor (GPCR) kinases (GRKs) play key role in homologous desensitization of GPCRs. GRKs phosphorylate activated receptors, promoting high affinity binding of arrestins, which precludes G protein coupling. Direct binding to active GPCRs activates GRKs, so that they selectively phosphorylate only the activated form of the receptor regardless of the accessibility...

GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1–2 September 2014

V. Gurevich, Daniel Fourmy, Vadim Cherezov, Fiona H. Marshall, R. Ian Storer, Isabel Moraes, Irina G. Tikhonova, Christofer S. Tautermann, Peter Hunt, Tom Ceska, Simon Hodgson, Mike J. Bodkin, Shweta ... 6GS , UK 3 C. S. Tautermann Boehringer Ingelheim Pharma GmbH & Co KG , Biberach , Germany 4 Alexander Heifetz , Gebhard F. X. Schertler, Roland Seifert, Christopher G. Tate, Patrick M. Sexton, Vsevolod

The Effect of Arrestin Conformation on the Recruitment of c-Raf1, MEK1, and ERK1/2 Activation

Arrestins are multifunctional signaling adaptors originally discovered as proteins that “arrest” G protein activation by G protein-coupled receptors (GPCRs). Recently GPCR complexes with arrestins have been proposed to activate G protein-independent signaling pathways. In particular, arrestin-dependent activation of extracellular signal-regulated kinase 1/2 (ERK1/2) has been...

Kinetics of Rhodopsin Deactivation and Its Role in Regulating Recovery and Reproducibility of Rod Photoresponse

The single photon response (SPR) in vertebrate phototransduction is regulated by the dynamics of R* during its lifetime, including the random number of phosphorylations, the catalytic activity and the random sojourn time at each phosphorylation level. Because of this randomness the electrical responses are expected to be inherently variable. However the SPR is highly reproducible...

Arrestins: ubiquitous regulators of cellular signaling pathways

Summary In vertebrates, the arrestins are a family of four proteins that regulate the signaling and trafficking of hundreds of different G-protein-coupled receptors (GPCRs). Arrestin homologs are also found in insects, protochordates and nematodes. Fungi and protists have related proteins but do not have true arrestins. Structural information is available only for free (unbound...

Progressive Reduction of its Expression in Rods Reveals Two Pools of Arrestin-1 in the Outer Segment with Different Roles in Photoresponse Recovery

Light-induced rhodopsin signaling is turned off with sub-second kinetics by rhodopsin phosphorylation followed by arrestin-1 binding. To test the availability of the arrestin-1 pool in dark-adapted outer segment (OS) for rhodopsin shutoff, we measured photoresponse recovery rates of mice with arrestin-1 content in the OS of 2.5%, 5%, 60%, and 100% of wild type (WT) level by two...