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Active Conformations of Arrestins: Expected and Unexpected Changes

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The Structural Basis of Arrestin Functions

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Abstract

The idea that the conformation of the receptor-bound arrestin is dramatically different from that of a free arrestin in solution emerged soon after the discovery of the first member of the family, visual arrestin-1. However, most of the evidence for this emerged in the last few years from studies using biophysical methods and X-ray crystallography. The similarity of the conformational changes in different arrestin subtypes detected by various methods suggests that these rearrangements accompany arrestin “activation”, i.e., the transition into the high-affinity receptor-binding state. The key changes include the release of the arrestin C-terminal tail, the twisting of the two arrestin domains relative to each other, and the changes in several flexible loops in the central “crest” on the receptor-binding surface and elsewhere in the molecule. From a signaling standpoint, the changes on the arrestin side not involved in receptor contact appear more important, as they allow the non-receptor partners to discriminate between free and receptor-bound forms of arrestins. The identification of these changes facilitates elucidation of the structural basis of arrestin-mediated signaling, including mapping the binding sites for various signaling proteins.

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Acknowledgements

This work was supported by the NIH RO1 EY011500, GM109955, GM077561 (VVG), EY05216 and the Jules Stein Professorship Endowment (WLH), and Canada Excellence Research Chairs program (OPE). OPE is the Anne and Max Tanenbaum Chair at University of Toronto. We thank Dr. Ned Van Eps for comments on the manuscript.

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Authors and Affiliations

  1. Department of Biochemistry, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Abhishek Bandyopadhyay & Oliver P. Ernst

  2. Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Ya Zhuo & Candice S. Klug

  3. University of California Los Angeles, Los Angeles, CA, 90095, USA

    Wayne L. Hubbell

  4. Department of Pharmacology, Vanderbilt University, 2200 Pierce Avenue, Preston Research Building, Rm. 454, Nashville, TN, 37232, USA

    Vsevolod V. Gurevich

  5. Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Oliver P. Ernst

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  1. Abhishek Bandyopadhyay
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  2. Ya Zhuo
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  3. Wayne L. Hubbell
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  4. Candice S. Klug
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  5. Vsevolod V. Gurevich
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  6. Oliver P. Ernst
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Correspondence to Candice S. Klug , Vsevolod V. Gurevich or Oliver P. Ernst .

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  1. Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA

    Vsevolod V. Gurevich

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Bandyopadhyay, A., Zhuo, Y., Hubbell, W.L., Klug, C.S., Gurevich, V.V., Ernst, O.P. (2017). Active Conformations of Arrestins: Expected and Unexpected Changes. In: Gurevich, V. (eds) The Structural Basis of Arrestin Functions. Springer, Cham. https://doi.org/10.1007/978-3-319-57553-7_12

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