Activation-dependent conformational changes in {beta}-arrestin 2 - PubMed

Affiliations

• PMID: 15501822
• DOI: 10.1074/jbc.M409785200

Free article

Activation-dependent conformational changes in {beta}-arrestin 2

Kunhong Xiao et al. J Biol Chem. 2004.

Free article

Abstract

Beta-arrestins are multifunctional adaptor proteins, which mediate desensitization, endocytosis, and alternate signaling pathways of seven membrane-spanning receptors (7MSRs). Crystal structures of the basal inactive state of visual arrestin (arrestin 1) and beta-arrestin 1 (arrestin 2) have been resolved. However, little is known about the conformational changes that occur in beta-arrestins upon binding to the activated phosphorylated receptor. Here we characterize the conformational changes in beta-arrestin 2 (arrestin 3) by comparing the limited tryptic proteolysis patterns and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) profiles of beta-arrestin 2 in the presence of a phosphopeptide (V(2)R-pp) derived from the C terminus of the vasopressin type II receptor (V(2)R) or the corresponding nonphosphopeptide (V(2)R-np). V(2)R-pp binds to beta-arrestin 2 specifically, whereas V(2)R-np does not. Activation of beta-arrestin 2 upon V(2)R-pp binding involves the release of its C terminus, as indicated by exposure of a previously inaccessible cleavage site, one of the polar core residues Arg(394), and rearrangement of its N terminus, as indicated by the shielding of a previously accessible cleavage site, residue Arg(8). Interestingly, binding of the polyanion heparin also leads to release of the C terminus of beta-arrestin 2; however, heparin and V(2)R-pp have different binding site(s) and/or induce different conformational changes in beta-arrestin 2. Release of the C terminus from the rest of beta-arrestin 2 has functional consequences in that it increases the accessibility of a clathrin binding site (previously demonstrated to lie between residues 371 and 379) thereby enhancing clathrin binding to beta-arrestin 2 by 10-fold. Thus, the V(2)R-pp can activate beta-arrestin 2 in vitro, most likely mimicking the effects of an activated phosphorylated 7MSR. These results provide the first direct evidence of conformational changes associated with the transition of beta-arrestin 2 from its basal inactive conformation to its biologically active conformation and establish a system in which receptor-beta-arrestin interactions can be modeled in vitro.

Similar articles

• The active conformation of beta-arrestin1: direct evidence for the phosphate sensor in the N-domain and conformational differences in the active states of beta-arrestins1 and -2.

  Nobles KN, Guan Z, Xiao K, Oas TG, Lefkowitz RJ. Nobles KN, et al. J Biol Chem. 2007 Jul 20;282(29):21370-81. doi: 10.1074/jbc.M611483200. Epub 2007 May 18. J Biol Chem. 2007. PMID: 17513300

• Conformational differences between arrestin2 and pre-activated mutants as revealed by hydrogen exchange mass spectrometry.

  Carter JM, Gurevich VV, Prossnitz ER, Engen JR. Carter JM, et al. J Mol Biol. 2005 Aug 26;351(4):865-78. doi: 10.1016/j.jmb.2005.06.048. J Mol Biol. 2005. PMID: 16045931

• Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide.

  Shukla AK, Manglik A, Kruse AC, Xiao K, Reis RI, Tseng WC, Staus DP, Hilger D, Uysal S, Huang LY, Paduch M, Tripathi-Shukla P, Koide A, Koide S, Weis WI, Kossiakoff AA, Kobilka BK, Lefkowitz RJ. Shukla AK, et al. Nature. 2013 May 2;497(7447):137-41. doi: 10.1038/nature12120. Epub 2013 Apr 21. Nature. 2013. PMID: 23604254 Free PMC article.

• β-arrestins and G protein-coupled receptor trafficking.

  Tian X, Kang DS, Benovic JL. Tian X, et al. Handb Exp Pharmacol. 2014;219:173-86. doi: 10.1007/978-3-642-41199-1_9. Handb Exp Pharmacol. 2014. PMID: 24292830 Free PMC article. Review.

• Beta-arrestin signaling and regulation of transcription.

  Ma L, Pei G. Ma L, et al. J Cell Sci. 2007 Jan 15;120(Pt 2):213-8. doi: 10.1242/jcs.03338. J Cell Sci. 2007. PMID: 17215450 Review.

Cited by

• The structural basis of arrestin-mediated regulation of G-protein-coupled receptors.

  Gurevich VV, Gurevich EV. Gurevich VV, et al. Pharmacol Ther. 2006 Jun;110(3):465-502. doi: 10.1016/j.pharmthera.2005.09.008. Epub 2006 Feb 3. Pharmacol Ther. 2006. PMID: 16460808 Free PMC article. Review.

• Differential interaction of spin-labeled arrestin with inactive and active phosphorhodopsin.

  Hanson SM, Francis DJ, Vishnivetskiy SA, Kolobova EA, Hubbell WL, Klug CS, Gurevich VV. Hanson SM, et al. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4900-5. doi: 10.1073/pnas.0600733103. Epub 2006 Mar 17. Proc Natl Acad Sci U S A. 2006. PMID: 16547131 Free PMC article.

• Custom-designed proteins as novel therapeutic tools? The case of arrestins.

  Gurevich VV, Gurevich EV. Gurevich VV, et al. Expert Rev Mol Med. 2010 Apr 23;12:e13. doi: 10.1017/S1462399410001444. Expert Rev Mol Med. 2010. PMID: 20412604 Free PMC article. Review.

• Double life: How GRK2 and β-arrestin signaling participate in diseases.

  Zhai R, Snyder J, Montgomery S, Sato PY. Zhai R, et al. Cell Signal. 2022 Jun;94:110333. doi: 10.1016/j.cellsig.2022.110333. Epub 2022 Apr 14. Cell Signal. 2022. PMID: 35430346 Free PMC article. Review.

• Extensive shape shifting underlies functional versatility of arrestins.

  Gurevich VV, Gurevich EV. Gurevich VV, et al. Curr Opin Cell Biol. 2014 Apr;27:1-9. doi: 10.1016/j.ceb.2013.10.007. Epub 2013 Nov 16. Curr Opin Cell Biol. 2014. PMID: 24680424 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • Addgene Non-profit plasmid repository

• Miscellaneous

  • NCI CPTAC Assay Portal