Insilico Homology Modeling of β-arrestin 2, a Suppressor of G-Protein Coupled Receptor Mediated Apoptosis

Abstract

The protein encoded by ARRB2 gene β-arrestin 2 also commonly known as β-arrestin is an intercellular protein that is thought to form complex with most of the phosphorylated G -protein coupled receptor (GPCR) and cause specific arresting of the cellular response to hormones and sensory signals. β-arrestin is expressed at higher levels in central nervous system and plays a major role in the cell signaling pathway and GPCR mediated apoptosis. The availability of the crystal structure of splice variant of Beta arrestin provide us with the valuable information for the homology modeling and Insilico drug design for suppressing the autoimmune diseases. The target template of protein for homology modeling was obtained from NCBI server accession number ABG47460, the template protein was obtained from PDB _nr95 ׀1G4M_A׀ ׀1SUJ_A׀ ׀1CF1_A׀ ׀2FGS_A׀ having identity of 71%,57%,48%,48%, E value 2.17334e-147, 2.23051e-115, 3.32073e-95, 3.24677 respectively. By multiple template modeling a comparative model of protein was prepared using DISCOVERY STUDIO CLIENT V2.5.0.9164. Further from Ramachandran Plot analysis using it was confirmed that the 94.6% of residues fall under the most favorable region. The 3D model was then further analyzed using Structural analysis and verification server.

Keywords: apoptosis, beta-arrestin, g-protein coupled receptor, homology modeling
REFERENCES
[1] Popov SG, Villasmil R, Bernardi J Lethal toxin of Bacillus anthracis causes apoptosis of macrophages. Biochem. Biophys. Res.Commun. April 2002; 293 (1): 349–55p.
[2] Brüne B. Nitric oxide: NO apoptosis or turning it ON? Cell Death Differ. August 2003; 10 (8): 864–9p.
[3] Luttrell LM, Lefkowitz RJ. The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci. 2002; 115: 455–465p.
[4] Eugenia V Gurevich, Vsevolod V Gurevich. Arrestins: ubiquitous regulators of cellular signaling pathways. Genome Biology. 2006; 7: 236p.
[5] Havard Attramadal, Jeffrey L. Arriza, Chiye Aoki, Ted M. Dawson, Juan Codina, Madan M. Kwatra, Solomon H. Snyder, Marc G. Caron, Robert J. Lefkowitz. β -Arrestin2, a Novel Member of the Arrestin/ β -Arrestin Gene Family. The Journal of Biologiccahle Mistry. September 5,1992; 267 (25): 17882–17890p.Martí-Renom MA, Stuart AC, Fiser A, Sánchez R, Melo F, Sali A. Comparative protein structure modeling of genes and genomes. Annu Rev. Biophys Biomol Struct. 2000; 29: 291–325p.
[6] Williamson AR. Creating a structural genomics consortium. Nat Struct Biol. 2000; 7(11s): 953p.
[7] Discovery Studio client V2.5.0.9164 Accelrys Software Inc; San Diego, CA USA
[8] Fiser A, Sali A. ModLoop: automated modeling of loops in protein structures. Bioinformatics. 2003 Dec 12; 19(18): 2500p.
[9] Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Cryst. 1993; 26: 283–291p.
[10] Lüthy R, Bowie JU, Eisenberg D. Assessment of protein models with three-dimensional profiles. Nature. 1992; 356 (6364): 83–85p.
[11] Tiziana Castrignano`, Paolo D’Onorio De Meo, Domenico Cozzetto,Ivano Giuseppe Talamo, Anna Tramontano. The PMDB Protein Model Database. Nucleic Acids Research. 2006; 34: D306–D309p.