Profile

We are interested in structure, function, and biology of arrestin proteins. Arrestins bind activated phosphorylated G protein-coupled receptors (GPCRs), thereby shutting down their signaling via G proteins (desensitization), targeting receptors for internalization. Free and receptor-bound arrestins are multi-functional signaling adapters, interacting with more than 20 signaling proteins, many of which play key role in "life-or-death" decisions in the cell. We want to understand the molecular mechanisms that arrestins use to "decide" when to bind particular interaction partners and when to dissociate. We have mapped receptor-arrestin interaction interface fairly well and we want to elucidate arrestin binding sites for its other interaction partners with the same precision. We intend to use this information to construct "custom-designed" arrestins that link the receptor of interest to the signaling pathway of our choosing. These tools will allow us to tell the cell what to do and when to do it. For example, "biased" arrestins can enhance pro-survival signaling, preventing cell death characteristic for neurodegenerative diseases (such as Alzheimer's, Parkinson's, or retinal degeneration), or tip the balance toward cell death, which would be useful to prevent uncontrolled proliferation characteristic for cancer.
The solution of the crystal structure of three arrestin proteins and elucidation of the mechanism of arrestin phosphate sensor action allowed us to construct arrestin mutants that bind the active form of their cognate GPCRs regardless of receptor phosphorylation. These "super-arrestins" may prove useful for gene therapy of disorders associated with excessive signaling by various GPCRs that range from night blindness and retinal degeneration to several forms of cancer. We are testing whether transgenic expression of phosphorylation-independent mutants of visual arrestin prevents retinal degeneration in several mouse models.
We believe that the combination of different approaches ranging from hard-core biochemical and biophysical methods and X-ray crystallography to cell culture and transgenic animals is necessary to answer biologically relevant questions concerning various facets of arrestin function and to create novel therapeutic tools based on this information.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Arrestins: structural disorder creates rich functionality. Gurevich VV, Gurevich EV, Uversky VN (2018) Protein Cell 9(12): 986-1003
    › Primary publication · 29453740 (PubMed) · PMC6251804 (PubMed Central)
  2. Molecular Defects of the Disease-Causing Human Arrestin-1 C147F Mutant. Vishnivetskiy SA, Sullivan LS, Bowne SJ, Daiger SP, Gurevich EV, Gurevich VV (2018) Invest Ophthalmol Vis Sci 59(1): 13-20
    › Primary publication · 29305604 (PubMed) · PMC5756042 (PubMed Central)
  3. Molecular Mechanisms of GPCR Signaling: A Structural Perspective. Gurevich VV, Gurevich EV (2017) Int J Mol Sci 18(12)
    › Primary publication · 29186792 (PubMed) · PMC5751122 (PubMed Central)
  4. Heterologous phosphorylation-induced formation of a stability lock permits regulation of inactive receptors by β-arrestins. Tóth AD, Prokop S, Gyombolai P, Várnai P, Balla A, Gurevich VV, Hunyady L, Turu G (2018) J Biol Chem 293(3): 876-892
    › Primary publication · 29146594 (PubMed) · PMC5777260 (PubMed Central)
  5. Non-visual arrestins regulate the focal adhesion formation via small GTPases RhoA and Rac1 independently of GPCRs. Cleghorn WM, Bulus N, Kook S, Gurevich VV, Zent R, Gurevich EV (2018) Cell Signal : 259-269
    › Primary publication · 29133163 (PubMed) · PMC5732042 (PubMed Central)
  6. Structural basis of arrestin-3 activation and signaling. Chen Q, Perry NA, Vishnivetskiy SA, Berndt S, Gilbert NC, Zhuo Y, Singh PK, Tholen J, Ohi MD, Gurevich EV, Brautigam CA, Klug CS, Gurevich VV, Iverson TM (2017) Nat Commun 8(1): 1427
    › Primary publication · 29127291 (PubMed) · PMC5681653 (PubMed Central)
  7. Using two-site binding models to analyze microscale thermophoresis data. Tso SC, Chen Q, Vishnivetskiy SA, Gurevich VV, Iverson TM, Brautigam CA (2018) Anal Biochem : 64-75
    › Primary publication · 29054528 (PubMed) · PMC5906060 (PubMed Central)
  8. Paradigm Shift is the Normal State of Pharmacology. Gurevich VV (2016) EC Pharmacol Toxicol 2(2): 80-85
    › Primary publication · 28936490 (PubMed) · PMC5604476 (PubMed Central)
  9. Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors. Zhou XE, He Y, de Waal PW, Gao X, Kang Y, Van Eps N, Yin Y, Pal K, Goswami D, White TA, Barty A, Latorraca NR, Chapman HN, Hubbell WL, Dror RO, Stevens RC, Cherezov V, Gurevich VV, Griffin PR, Ernst OP, Melcher K, Xu HE (2017) Cell 170(3): 457-469.e13
    › Primary publication · 28753425 (PubMed) · PMC5567868 (PubMed Central)
  10. Uncovering missing pieces: duplication and deletion history of arrestins in deuterostomes. Indrischek H, Prohaska SJ, Gurevich VV, Gurevich EV, Stadler PF (2017) BMC Evol Biol 17(1): 163
    › Primary publication · 28683816 (PubMed) · PMC5501109 (PubMed Central)
  11. Hepatic β-arrestin 2 is essential for maintaining euglycemia. Zhu L, Rossi M, Cui Y, Lee RJ, Sakamoto W, Perry NA, Urs NM, Caron MG, Gurevich VV, Godlewski G, Kunos G, Chen M, Chen W, Wess J (2017) J Clin Invest 127(8): 2941-2945
    › Primary publication · 28650340 (PubMed) · PMC5531395 (PubMed Central)
  12. A Novel Dominant Mutation in SAG, the Arrestin-1 Gene, Is a Common Cause of Retinitis Pigmentosa in Hispanic Families in the Southwestern United States. Sullivan LS, Bowne SJ, Koboldt DC, Cadena EL, Heckenlively JR, Branham KE, Wheaton DH, Jones KD, Ruiz RS, Pennesi ME, Yang P, Davis-Boozer D, Northrup H, Gurevich VV, Chen R, Xu M, Li Y, Birch DG, Daiger SP (2017) Invest Ophthalmol Vis Sci 58(5): 2774-2784
    › Primary publication · 28549094 (PubMed) · PMC5455168 (PubMed Central)
  13. Functional role of the three conserved cysteines in the N domain of visual arrestin-1. Vishnivetskiy SA, Lee RJ, Zhou XE, Franz A, Xu Q, Xu HE, Gurevich VV (2017) J Biol Chem 292(30): 12496-12502
    › Primary publication · 28536260 (PubMed) · PMC5535024 (PubMed Central)
  14. Differential manipulation of arrestin-3 binding to basal and agonist-activated G protein-coupled receptors. Prokop S, Perry NA, Vishnivetskiy SA, Toth AD, Inoue A, Milligan G, Iverson TM, Hunyady L, Gurevich VV (2017) Cell Signal : 98-107
    › Primary publication · 28461104 (PubMed) · PMC5797668 (PubMed Central)
  15. Arrestin-2 and arrestin-3 differentially modulate locomotor responses and sensitization to amphetamine. Zurkovsky L, Sedaghat K, Ahmed MR, Gurevich VV, Gurevich EV (2017) Neuropharmacology : 20-29
    › Primary publication · 28419873 (PubMed) · PMC5859313 (PubMed Central)
  16. β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions. 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 (2017) Nat Commun : 14295
    › Primary publication · 28145434 (PubMed) · PMC5296650 (PubMed Central)
  17. C-terminal motif of human neuropeptide Y receptor determines internalization and arrestin recruitment. Wanka L, Babilon S, Burkert K, Mörl K, Gurevich VV, Beck-Sickinger AG (2017) Cell Signal : 233-239
    › Primary publication · 27818291 (PubMed) · PMC5797669 (PubMed Central)
  18. G protein-coupled receptor kinases as regulators of dopamine receptor functions. Gurevich EV, Gainetdinov RR, Gurevich VV (2016) Pharmacol Res : 1-16
    › Primary publication · 27178731 (PubMed) · PMC5079267 (PubMed Central)
  19. Peptide mini-scaffold facilitates JNK3 activation in cells. Zhan X, Stoy H, Kaoud TS, Perry NA, Chen Q, Perez A, Els-Heindl S, Slagis JV, Iverson TM, Beck-Sickinger AG, Gurevich EV, Dalby KN, Gurevich VV (2016) Sci Rep : 21025
    › Primary publication · 26868142 (PubMed) · PMC4751492 (PubMed Central)
  20. A G Protein-biased Designer G Protein-coupled Receptor Useful for Studying the Physiological Relevance of Gq/11-dependent Signaling Pathways. Hu J, Stern M, Gimenez LE, Wanka L, Zhu L, Rossi M, Meister J, Inoue A, Beck-Sickinger AG, Gurevich VV, Wess J (2016) J Biol Chem 291(15): 7809-20
    › Primary publication · 26851281 (PubMed) · PMC4824988 (PubMed Central)
  21. Analyzing the roles of multi-functional proteins in cells: The case of arrestins and GRKs. Gurevich VV, Gurevich EV (2015) Crit Rev Biochem Mol Biol 50(5): 440-52
    › Primary publication · 26453028 (PubMed) · PMC4852696 (PubMed Central)
  22. Influence of Arrestin on the Photodecay of Bovine Rhodopsin. Chatterjee D, Eckert CE, Slavov C, Saxena K, Fürtig B, Sanders CR, Gurevich VV, Wachtveitl J, Schwalbe H (2015) Angew Chem Int Ed Engl 54(46): 13555-60
    › Primary publication · 26383645 (PubMed) · PMC4685475 (PubMed Central)
  23. Using Bioluminescence Resonance Energy Transfer (BRET) to Characterize Agonist-Induced Arrestin Recruitment to Modified and Unmodified G Protein-Coupled Receptors. Donthamsetti P, Quejada JR, Javitch JA, Gurevich VV, Lambert NA (2015) Curr Protoc Pharmacol : 2.14.1-14
    › Primary publication · 26331887 (PubMed) · PMC4583203 (PubMed Central)
  24. How genetic errors in GPCRs affect their function: Possible therapeutic strategies. Stoy H, Gurevich VV (2015) Genes Dis 2(2): 108-132
    › Primary publication · 26229975 (PubMed) · PMC4516391 (PubMed Central)
  25. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Kang Y, Zhou XE, Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Ke J, Tan MH, Zhang C, Moeller A, West GM, Pascal BD, Van Eps N, Caro LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi X, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhury S, Conrad CE, Coe J, Liu H, Lisova S, Kupitz C, Grotjohann I, Fromme R, Jiang Y, Tan M, Yang H, Li J, Wang M, Zheng Z, Li D, Howe N, Zhao Y, Standfuss J, Diederichs K, Dong Y, Potter CS, Carragher B, Caffrey M, Jiang H, Chapman HN, Spence JC, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE (2015) Nature 523(7562): 561-7
    › Primary publication · 26200343 (PubMed) · PMC4521999 (PubMed Central)
  26. Quantitative Signaling and Structure-Activity Analyses Demonstrate Functional Selectivity at the Nociceptin/Orphanin FQ Opioid Receptor. Chang SD, Mascarella SW, Spangler SM, Gurevich VV, Navarro HA, Carroll FI, Bruchas MR (2015) Mol Pharmacol 88(3): 502-11
    › Primary publication · 26134494 (PubMed) · PMC4551045 (PubMed Central)
  27. G Protein-Coupled Receptor Kinase 2 (GRK2) and 5 (GRK5) Exhibit Selective Phosphorylation of the Neurotensin Receptor in Vitro. Inagaki S, Ghirlando R, Vishnivetskiy SA, Homan KT, White JF, Tesmer JJ, Gurevich VV, Grisshammer R (2015) Biochemistry 54(28): 4320-9
    › Primary publication · 26120872 (PubMed) · PMC4512254 (PubMed Central)
  28. Arrestins: Critical Players in Trafficking of Many GPCRs. Gurevich VV, Gurevich EV (2015) Prog Mol Biol Transl Sci : 1-14
    › Primary publication · 26055052 (PubMed) · PMC5841159 (PubMed Central)
  29. GRK3 suppresses L-DOPA-induced dyskinesia in the rat model of Parkinson's disease via its RGS homology domain. Ahmed MR, Bychkov E, Li L, Gurevich VV, Gurevich EV (2015) Sci Rep : 10920
    › Primary publication · 26043205 (PubMed) · PMC4455246 (PubMed Central)
  30. C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor. Azevedo AW, Doan T, Moaven H, Sokal I, Baameur F, Vishnivetskiy SA, Homan KT, Tesmer JJ, Gurevich VV, Chen J, Rieke F (2015) Elife
    › Primary publication · 25910054 (PubMed) · PMC4438306 (PubMed Central)
  31. GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1-2 September 2014. Heifetz A, Schertler GF, Seifert R, Tate CG, Sexton PM, Gurevich VV, Fourmy D, Cherezov V, Marshall FH, Storer RI, Moraes I, Tikhonova IG, Tautermann CS, Hunt P, Ceska T, Hodgson S, Bodkin MJ, Singh S, Law RJ, Biggin PC (2015) Naunyn Schmiedebergs Arch Pharmacol 388(8): 883-903
    › Primary publication · 25772061 (PubMed) · PMC4495723 (PubMed Central)
  32. G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs). Li L, Homan KT, Vishnivetskiy SA, Manglik A, Tesmer JJ, Gurevich VV, Gurevich EV (2015) J Biol Chem 290(17): 10775-90
    › Primary publication · 25770216 (PubMed) · PMC4409243 (PubMed Central)
  33. Arrestin-3-Dependent Activation of c-Jun N-Terminal Kinases (JNKs). Zhan X, Kook S, Kaoud TS, Dalby KN, Gurevich EV, Gurevich VV (2015) Curr Protoc Pharmacol : 2.12.1-2.12.26
    › Primary publication · 25737158 (PubMed) · PMC4361079 (PubMed Central)
  34. The rhodopsin-arrestin-1 interaction in bicelles. Chen Q, Vishnivetskiy SA, Zhuang T, Cho MK, Thaker TM, Sanders CR, Gurevich VV, Iverson TM (2015) Methods Mol Biol : 77-95
    › Primary publication · 25697518 (PubMed) · PMC4520306 (PubMed Central)
  35. Beyond traditional pharmacology: new tools and approaches. Gurevich EV, Gurevich VV (2015) Br J Pharmacol 172(13): 3229-41
    › Primary publication · 25572005 (PubMed) · PMC4500362 (PubMed Central)
  36. Arrestins regulate cell spreading and motility via focal adhesion dynamics. Cleghorn WM, Branch KM, Kook S, Arnette C, Bulus N, Zent R, Kaverina I, Gurevich EV, Weaver AM, Gurevich VV (2015) Mol Biol Cell 26(4): 622-35
    › Primary publication · 25540425 (PubMed) · PMC4325834 (PubMed Central)
  37. Arrestin expression in E. coli and purification. Vishnivetskiy SA, Zhan X, Chen Q, Iverson TM, Gurevich VV (2014) Curr Protoc Pharmacol : Unit 2.11.1-19
    › Primary publication · 25446290 (PubMed) · PMC4260927 (PubMed Central)
  38. Overview of different mechanisms of arrestin-mediated signaling. Gurevich VV, Gurevich EV (2014) Curr Protoc Pharmacol : Unit 2.10.1-9
    › Primary publication · 25446289 (PubMed) · PMC4260930 (PubMed Central)
  39. Development of an MRI biomarker sensitive to tetrameric visual arrestin 1 and its reduction via light-evoked translocation in vivo. Berkowitz BA, Gorgis J, Patel A, Baameur F, Gurevich VV, Craft CM, Kefalov VJ, Roberts R (2015) FASEB J 29(2): 554-64
    › Primary publication · 25351983 (PubMed) · PMC4314227 (PubMed Central)
  40. Peptide modifications differentially alter G protein-coupled receptor internalization and signaling bias. Mäde V, Babilon S, Jolly N, Wanka L, Bellmann-Sickert K, Diaz Gimenez LE, Mörl K, Cox HM, Gurevich VV, Beck-Sickinger AG (2014) Angew Chem Int Ed Engl 53(38): 10067-71
    › Primary publication · 25065900 (PubMed) · PMC4704863 (PubMed Central)
  41. Identification of receptor binding-induced conformational changes in non-visual arrestins. Zhuo Y, Vishnivetskiy SA, Zhan X, Gurevich VV, Klug CS (2014) J Biol Chem 289(30): 20991-1002
    › Primary publication · 24867953 (PubMed) · PMC4110305 (PubMed Central)
  42. Mutations in arrestin-3 differentially affect binding to neuropeptide Y receptor subtypes. Gimenez LE, Babilon S, Wanka L, Beck-Sickinger AG, Gurevich VV (2014) Cell Signal 26(7): 1523-31
    › Primary publication · 24686081 (PubMed) · PMC4033671 (PubMed Central)
  43. Extensive shape shifting underlies functional versatility of arrestins. Gurevich VV, Gurevich EV (2014) Curr Opin Cell Biol : 1-9
    › Primary publication · 24680424 (PubMed) · PMC3971385 (PubMed Central)
  44. Arrestin makes T cells stop and become active. Gurevich VV, Gurevich EV (2014) EMBO J 33(6): 531-3
    › Primary publication · 24502974 (PubMed) · PMC3989646 (PubMed Central)
  45. Arrestin-3 binds the MAP kinase JNK3α2 via multiple sites on both domains. Zhan X, Perez A, Gimenez LE, Vishnivetskiy SA, Gurevich VV (2014) Cell Signal 26(4): 766-76
    › Primary publication · 24412749 (PubMed) · PMC3936466 (PubMed Central)
  46. Arrestins in apoptosis. Kook S, Gurevich VV, Gurevich EV (2014) Handb Exp Pharmacol : 309-39
    › Primary publication · 24292837 (PubMed) · PMC4516163 (PubMed Central)
  47. Arrestin-dependent activation of JNK family kinases. Zhan X, Kook S, Gurevich EV, Gurevich VV (2014) Handb Exp Pharmacol : 259-80
    › Primary publication · 24292834 (PubMed) · PMC4514028 (PubMed Central)
  48. Self-association of arrestin family members. Chen Q, Zhuo Y, Kim M, Hanson SM, Francis DJ, Vishnivetskiy SA, Altenbach C, Klug CS, Hubbell WL, Gurevich VV (2014) Handb Exp Pharmacol : 205-23
    › Primary publication · 24292832 (PubMed) · PMC4512752 (PubMed Central)
  49. Targeting individual GPCRs with redesigned nonvisual arrestins. Gimenez LE, Vishnivetskiy SA, Gurevich VV (2014) Handb Exp Pharmacol : 153-70
    › Primary publication · 24292829 (PubMed) · PMC4516156 (PubMed Central)
  50. Enhanced phosphorylation-independent arrestins and gene therapy. Gurevich VV, Song X, Vishnivetskiy SA, Gurevich EV (2014) Handb Exp Pharmacol : 133-52
    › Primary publication · 24292828 (PubMed) · PMC4516159 (PubMed Central)
  51. Therapeutic potential of small molecules and engineered proteins. Gurevich EV, Gurevich VV (2014) Handb Exp Pharmacol : 1-12
    › Primary publication · 24292822 (PubMed) · PMC4513659 (PubMed Central)
  52. Arrestin-3 binds c-Jun N-terminal kinase 1 (JNK1) and JNK2 and facilitates the activation of these ubiquitous JNK isoforms in cells via scaffolding. Kook S, Zhan X, Kaoud TS, Dalby KN, Gurevich VV, Gurevich EV (2013) J Biol Chem 288(52): 37332-42
    › Primary publication · 24257757 (PubMed) · PMC3873585 (PubMed Central)
  53. Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release and cell death. Kook S, Zhan X, Cleghorn WM, Benovic JL, Gurevich VV, Gurevich EV (2014) Cell Death Differ 21(1): 172-84
    › Primary publication · 24141717 (PubMed) · PMC3857626 (PubMed Central)
  54. Visual arrestin interaction with clathrin adaptor AP-2 regulates photoreceptor survival in the vertebrate retina. Moaven H, Koike Y, Jao CC, Gurevich VV, Langen R, Chen J (2013) Proc Natl Acad Sci U S A 110(23): 9463-8
    › Primary publication · 23690606 (PubMed) · PMC3677467 (PubMed Central)
  55. Insights into congenital stationary night blindness based on the structure of G90D rhodopsin. Singhal A, Ostermaier MK, Vishnivetskiy SA, Panneels V, Homan KT, Tesmer JJ, Veprintsev D, Deupi X, Gurevich VV, Schertler GF, Standfuss J (2013) EMBO Rep 14(6): 520-6
    › Primary publication · 23579341 (PubMed) · PMC3674435 (PubMed Central)
  56. Identification of phosphorylation sites in the COOH-terminal tail of the μ-opioid receptor. Chen YJ, Oldfield S, Butcher AJ, Tobin AB, Saxena K, Gurevich VV, Benovic JL, Henderson G, Kelly E (2013) J Neurochem 124(2): 189-99
    › Primary publication · 23106126 (PubMed) · PMC4226418 (PubMed Central)
  57. Conformation of receptor-bound visual arrestin. Kim M, Vishnivetskiy SA, Van Eps N, Alexander NS, Cleghorn WM, Zhan X, Hanson SM, Morizumi T, Ernst OP, Meiler J, Gurevich VV, Hubbell WL (2012) Proc Natl Acad Sci U S A 109(45): 18407-12
    › Primary publication · 23091036 (PubMed) · PMC3494953 (PubMed Central)
  58. Ligand directed signaling differences between rodent and human κ-opioid receptors. Schattauer SS, Miyatake M, Shankar H, Zietz C, Levin JR, Liu-Chen LY, Gurevich VV, Rieder MJ, Chavkin C (2012) J Biol Chem 287(50): 41595-607
    › Primary publication · 23086943 (PubMed) · PMC3516711 (PubMed Central)