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Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2.

<div class='caption-title'>Binding affinities and structures of arrestin2 in complex with four different phosphobarcodes.</div>
<div class='caption-title'>Phosphopeptides induce arrestin to form an active conformation.</div>
<div class='caption-title'>Structure of the arrestin2-V2Rpp-1 complex and correlation of phospho-binding at the V1 site with the conformational change related to the c-Raf-1 interaction.</div>
He QT, Xiao P, Huang SM, Jia YL, Zhu ZL, Lin JY, Yang F, Tao XN, Zhao RJ, Gao FY, Niu XG, Xiao KH, Wang J, Jin C, Sun JP, Yu X
OpenAccess logo Nat Commun 12 2396 (2021)
Related entries: 7dfa, 7dfb, 7dfc

Cited: 22 times
EuropePMC logo PMID: 33888704

Abstract

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.

Articles - 7df9 mentioned but not cited (1)

  1. Surveying nonvisual arrestins reveals allosteric interactions between functional sites. Seckler JM, Robinson EN, Lewis SJ, Grossfield A. Proteins 91 99-107 (2023)


Reviews citing this publication (8)

  1. G protein-coupled receptor signaling: transducers and effectors. Jiang H, Galtes D, Wang J, Rockman HA. Am J Physiol Cell Physiol 323 C731-C748 (2022)
  2. G protein-coupled receptor interactions with arrestins and GPCR kinases: The unresolved issue of signal bias. Chen Q, Tesmer JJG. J Biol Chem 298 102279 (2022)
  3. Emerging structural insights into GPCR-β-arrestin interaction and functional outcomes. Maharana J, Banerjee R, Yadav MK, Sarma P, Shukla AK. Curr Opin Struct Biol 75 102406 (2022)
  4. QR code model: a new possibility for GPCR phosphorylation recognition. Chen H, Zhang S, Zhang X, Liu H. Cell Commun Signal 20 23 (2022)
  5. Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins. Kim K, Han Y, Duan L, Chung KY. Int J Mol Sci 23 1000 (2022)
  6. Accelerated Multiphosphorylated Peptide Synthesis. Grunhaus D, Molina ER, Cohen R, Stein T, Friedler A, Hurevich M. Org Process Res Dev 26 2492-2497 (2022)
  7. Post-Translational Modifications of G Protein-Coupled Receptors Revealed by Proteomics and Structural Biology. Zhang B, Li S, Shui W. Front Chem 10 843502 (2022)
  8. Structure, function and drug discovery of GPCR signaling. Cheng L, Xia F, Li Z, Shen C, Yang Z, Hou H, Sun S, Feng Y, Yong X, Tian X, Qin H, Yan W, Shao Z. Mol Biomed 4 46 (2023)

Articles citing this publication (13)

  1. Activation pathway of a G protein-coupled receptor uncovers conformational intermediates as targets for allosteric drug design. Lu S, He X, Yang Z, Chai Z, Zhou S, Wang J, Rehman AU, Ni D, Pu J, Sun J, Zhang J. Nat Commun 12 4721 (2021)
  2. Tethered peptide activation mechanism of the adhesion GPCRs ADGRG2 and ADGRG4. Xiao P, Guo S, Wen X, He QT, Lin H, Huang SM, Gou L, Zhang C, Yang Z, Zhong YN, Yang CC, Li Y, Gong Z, Tao XN, Yang ZS, Lu Y, Li SL, He JY, Wang C, Zhang L, Kong L, Sun JP, Yu X. Nature 604 771-778 (2022)
  3. Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD. Cao C, Barros-Álvarez X, Zhang S, Kim K, Dämgen MA, Panova O, Suomivuori CM, Fay JF, Zhong X, Krumm BE, Gumpper RH, Seven AB, Robertson MJ, Krogan NJ, Hüttenhain R, Nichols DE, Dror RO, Skiniotis G, Roth BL. Neuron 110 3154-3167.e7 (2022)
  4. Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease. Scarpa M, Molloy C, Jenkins L, Strellis B, Budgett RF, Hesse S, Dwomoh L, Marsango S, Tejeda GS, Rossi M, Ahmed Z, Milligan G, Hudson BD, Tobin AB, Bradley SJ. Proc Natl Acad Sci U S A 118 e2107389118 (2021)
  5. The Two Non-Visual Arrestins Engage ERK2 Differently. Perry-Hauser NA, Hopkins JB, Zhuo Y, Zheng C, Perez I, Schultz KM, Vishnivetskiy SA, Kaya AI, Sharma P, Dalby KN, Chung KY, Klug CS, Gurevich VV, Iverson TM. J Mol Biol 434 167465 (2022)
  6. Allosteric modulation of GPCR-induced β-arrestin trafficking and signaling by a synthetic intrabody. Baidya M, Chaturvedi M, Dwivedi-Agnihotri H, Ranjan A, Devost D, Namkung Y, Stepniewski TM, Pandey S, Baruah M, Panigrahi B, Sarma P, Yadav MK, Maharana J, Banerjee R, Kawakami K, Inoue A, Selent J, Laporte SA, Hébert TE, Shukla AK. Nat Commun 13 4634 (2022)
  7. The GPCR-β-arrestin complex allosterically activates C-Raf by binding its amino terminus. Zang Y, Kahsai AW, Pakharukova N, Huang LY, Lefkowitz RJ. J Biol Chem 297 101369 (2021)
  8. G protein-biased GPR3 signaling ameliorates amyloid pathology in a preclinical Alzheimer's disease mouse model. Huang Y, Rafael Guimarães T, Todd N, Ferguson C, Weiss KM, Stauffer FR, McDermott B, Hurtle BT, Saito T, Saido TC, MacDonald ML, Homanics GE, Thathiah A. Proc Natl Acad Sci U S A 119 e2204828119 (2022)
  9. Phosphorylation barcodes direct biased chemokine signaling at CXCR3. Eiger DS, Smith JS, Shi T, Stepniewski TM, Tsai CF, Honeycutt C, Boldizsar N, Gardner J, Nicora CD, Moghieb AM, Kawakami K, Choi I, Hicks C, Zheng K, Warman A, Alagesan P, Knape NM, Huang O, Silverman JD, Smith RD, Inoue A, Selent J, Jacobs JM, Rajagopal S. Cell Chem Biol 30 362-382.e8 (2023)
  10. The Role of ICL1 and H8 in Class B1 GPCRs; Implications for Receptor Activation. Winfield I, Barkan K, Routledge S, Robertson NJ, Harris M, Jazayeri A, Simms J, Reynolds CA, Poyner DR, Ladds G. Front Endocrinol (Lausanne) 12 792912 (2021)
  11. Distinct activation mechanisms of β-arrestin-1 revealed by 19F NMR spectroscopy. Zhai R, Wang Z, Chai Z, Niu X, Li C, Jin C, Hu Y. Nat Commun 14 7865 (2023)
  12. GPCR kinases generate an APH1A phosphorylation barcode to regulate amyloid-β generation. Todd NK, Huang Y, Lee JY, Doruker P, Krieger JM, Salisbury R, MacDonald M, Bahar I, Thathiah A. Cell Rep 40 111110 (2022)
  13. GPCR targeting of E3 ubiquitin ligase MDM2 by inactive β-arrestin. Yun Y, Yoon HJ, Jeong Y, Choi Y, Jang S, Chung KY, Lee HH. Proc Natl Acad Sci U S A 120 e2301934120 (2023)


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