Homology modelling of Frizzled 1 CRD and understanding the mechanism of Wnt mediated dimerization

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Homology modelling of Frizzled 1 CRD and understanding the mechanism of Wnt mediated dimerization

Author Affiliations

¹Deptt of Biotech, N.C. College of Engg, Israna Panipat, INDIA
²Centre of Bioinformatics, Central Univ of Punjab, Bhatinda, INDIA
³Deptt of Biotech, UIET, MDU, Rohtak, INDIA

Int. Res. J. Biological Sci., Volume 3, Issue (8), Pages 12-15, August,10 (2014)

Abstract

Frizzled is a family of G protein-coupled receptor serve as receptors in the Wnt signaling pathway. The usual length of frizzled proteins is about 600 amino acids. The N- terminus comprises of cysteine rich domain (CRD) and is extracellular. The CRD is followed by a lipopathic flexible region of 40-100 residues. The transmembrane part of frizzled protein consists of seven transmembrane -helices that form hydrophobic domains and are considered as a typical G protein-coupled receptors (GPCRs). The Frizzled and Wnt interaction is imperative for the signal transduction involving catenin protein. To understand the Wnt and Frizzled interaction a protocol was developed for the comparative model generation. The human Frizzled receptor (Fz1) has been studied and homology based structure model is proposed. The model was exhaustively checked on various parameters and was found to be of good quality. On the surface of Cysteine Rich Domain important sites were identified that could potentially play a role in Wnt mediated dimerisation of Frizzled receptors.

References

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[ref1] Cadigan K. and Liu Y., Wnt signaling: complexity at the surface, J Cell Sci., 119(Pt 3), 395-402 (2006)

[ref2] Chen X. and Deng Y., Simulations of a specific inhibitor of the dishevelled PDZ domain, J Mol Model., 15(1), 91-69 (2007)

[ref3] Cong F.L., Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP Development.,131(20), 5103-15(2004)

[ref4] Huang H. and Klein P., The Frizzled family: receptors for multiple signal transduction pathways, Genome Biol., 5(7),234 (2004)

[ref5] Jenny A. , Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled Binding, Nat Cell Biol., 7(7), 691-70 (2005)

[ref6] Melchior K., The WNT receptor FZD7 contributes to self-renewal signaling of human embryonic stemcells, Biol Chem., 389(7), 897-903 (2006)

[ref7] Zeng X.H., Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 hosphorylation/activation via frizzled, dishevelled and axin functions, Development, 135(2), 367-75 (2008)

[ref8] Thompson J.D., Higgins D.G., Gibson T.J., CLUSTAL W improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position specificgap penalties and weight matrix choice, Nucleic Acids Res., 22(22), 4673-80 (1994)

[ref9] Dhar D.V., Tanuj S., Kumar M.S. and Kumar P.A., Insights to Sequence Information of Lactoylglutathione Lyase Enzyme from Different Source Organisms, I. Res. J.Biological Sci., 1(6), 38-42 (2012)

[ref10] Manderville R.A., Synthesis, proton-affinity and anticancer properties of the prodigiosin-group naturalproducts, Curr Med Chem Anticancer Agents, ., 195–218 (2001)

[ref11] Perez-Tomas R., Montaner B., Llagostera E. and SotoCerrato V., The prodigiosins, proapoptotic drugs with anticancer properties, Biochem Pharmaco., 66, 1447 – 52(2003)

[ref12] Rich A.M., Nataatmadja M.I. and Reade P.C., Basal cell nuclear size in experimental oral mucosal carcinogenesis, Br. J. Cancer, 64, 96–98 (1991)

[ref13] http://pubchem.ncbi.nlm.nih.gov/ (2012)

[ref14] http://www.ebi.ac.uk/Tools/services/web/toolform.ebi?tool=tcoffee (2012)

[ref15] http://zinc.docking.org/ (2012)

[ref16] Gothoskar S.V. and Ranadive K.J., Anticancer screening of SAN-AB; an extract of marking nut, Semicarps anacardium, Indian J Exp Biol, 372- 375 (1971)

[ref17] Dwivedi V.D., Arora S., Kumar A. and Mishra S.K., Computational analysis of xanthine dehydrogenase enzyme from different source organisms, Network Modeling Analysis in Health Informatics and Bioinformatics, DOI :10.1007/s13721-013-0029-7 (2012)

[ref18] Rich A.M., Nataatmadja M.I. and Reade P.C., Basal cell nuclear size in experimental oral mucosal carcinogenesis,Br. J. Cancer, 64, 96–98 (I991)