Homology modeling and functional annotation of bubaline pregnancy associated glycoprotein 2

Journal of Animal Science and Biotechnology

Shiv Prasad¹  Bhaskar Ganguly² 

[1] Department of Animal Reproduction, Gynecology and Obstetrics, College of Veterinary and Animal Sciences, G. B. Pant University of Agriculture and Technology, Pantnagar, PIN: 263145, India;Department of Veterinary Physiology and Biochemistry, College of Veterinary and Animal Sciences, G. B. Pant University of Agriculture and Technology, Pantnagar, PIN: 263145, India

关键词: Function;    Structure;    Pregnancy associated glycoprotein (PAG);    Homology modeling;    Bubaline;   

Others  :  814216
DOI  :  10.1186/2049-1891-3-13

 received in 2012-01-21, accepted in 2012-05-09,  发布年份 2012

【 摘 要 】

Background

Pregnancy associated glycoproteins form a diverse family of glycoproteins that are variably expressed at different stages of gestation. They are probably involved in immunosuppression of the dam against the feto-maternal placentome. The presence of the products of binucleate cells in maternal circulation has also been correlated with placentogenesis and placental re-modeling. The exact structure and function of the gene product is unknown due to limitations on obtaining purified pregnancy associated glycoprotein preparations.

Results

Our study describes an in silico derived 3D model for bubaline pregnancy associated glycoprotein 2. Structure-activity features of the protein were characterized, and functional studies predict bubaline pregnancy associated glycoprotein 2 as an inducible, extra-cellular, non-essential, N-glycosylated, aspartic pro-endopeptidase that is involved in down-regulation of complement pathway and immunity during pregnancy. The protein is also predicted to be involved in nutritional processes, and apoptotic processes underlying fetal morphogenesis and re-modeling of feto-maternal tissues.

Conclusion

The structural and functional annotation of buPAG2 shall allow the designing of mutants and inhibitors for dissection of the exact physiological role of the protein.

【 授权许可】

   
2012 Ganguly and Prasad; licensee BioMed Central Ltd

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Butler JE, Hamilton WC, Sasser RG, Ruder CA, Hass GM, Williams RJ: Detection and partial characterization of two bovine pregnancy-specific proteins. Biol Reprod 1982, 26:925-933.
• [2]Zoli AP, Beckers JF, Wouters-Ballman P, Closset J, Falmagne P, Ectors F: Purification and characterization of a bovine pregnancy-associated glycoprotein. Biol Reprod 1991, 45:1-10.
• [3]Garbayo JM, Green JA, Mannikam M, Beckers JF, Kiesling DO, Early AD, Roberts M: Caprine pregnancy associated glycoproteins (PAG): their cloning, expression and evolutionary relationship to other PAG. Mol Reprod Dev 2000, 57:311-322.
• [4]Hashizume K, Ushizawa K, Patel OV, Kizaki K, Imai K, Yamada O, Nakano H, Takahashi T: Gene expression and maintenance of pregnancy in bovine roles of trophoblastic binucleate cell specific molecules. Reprod Fert Dev 2007, 19:79-90.
• [5]Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL: GenBank. Nucleic Acids Res 2007, 35:21-25.
• [6]Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR: Appel RD. Protein Identification and Analysis Tools on the ExPASy Server. In The Proteomics Protocols Handbook. Edited by Walker JM. Humana Press, Bairoch A; 2005:571-607.
• [7]Altschul SF, Madden TL, Schaeffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25:3389-3402.
• [8]Sali A, Potterton L, Yuan F, van Vlijmen H, Karplus M: Evaluation of comparative protein modeling by MODELLER. Proteins 1995, 23:318-326.
• [9]Guex N, Peitsch MC: SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modelling. Electrophoresis 1997, 18:2714-2723.
• [10]van Gunsteren WF, et al.: Biomolecular Simulation: The GROMOS96 Manual and User Guide. Vdf Hochschulverlag ETHZ, ; 1996:1-1042.
• [11]Vriend G: WHAT IF: A molecular modeling and drug design program. J Mol Graph 1990, 8:2-56.
• [12]Laskowski RA, Hutchinson EG, Michie AD, Wallace AC, Jones ML, Thornton JM: PDBsum: a Web-based database of summaries and analyses of all PDB structures. Trends Biochem Sci 1997, 22:488-490.
• [13]Colovos C, Yeates TO: Verification of protein structures: patterns of non bonded atomic interactions. Protein Sci 1993, 2:1511-1519.
• [14]Krieger E, Koraimann G, Vriend G: Increasing the precision of comparative models with YASARA NOVA - a self-parameterizing force field. Proteins 2002, 47:393-402.
• [15]Konagurthu AS, Whisstock JC, Stuckey PJ, Lesk AM: MUSTANG: A multiple structural alignment algorithm. Proteins 2006, 64:559-574.
• [16]Gupta R, Brunak S: Prediction of glycosylation across the human proteome and the correlation to protein function. Pacific Symposium on Biocomputing 2002, 7:310-322.
• [17]Petersen TN, Brunak S, von Heijne G, Nielsen H: SignalP 4.0: Discriminating signal peptides from transmembrane regions. Nature Methods 2011, 8:785-786.
• [18]Castrignanò T, De Meo PD, Cozzetto D, Talamo IG, Tramontano A: The PMDB Protein Model Database. Nucleic Acids Res 2006, 34(Database issue):D306-D309.
• [19]Zdobnov EM, Apweiler R: InterProScan - an integration platform for the signature-recognition methods in InterPro. Bioinformatics 2001, 17:847-848.
• [20]Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer EL, Eddy SR, Bateman A: The Pfam protein families database. Nucleic Acids Res 2010, 38(Database issue):D211-D222.
• [21]Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Lu F, Marchler GH, Mullokandov M, Omelchenko MV, Robertson CL, Song JS, Thanki N, Yamashita RA, Zhang D, Zhang N, Zheng C, Bryant SH: CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res 2011, 39(Database issue):D225-D229.
• [22]Pal D, Eisenberg D: Inference of protein function from protein structure. Structure 2005, 13:121-130.
• [23]Hawkins T, Luban S, Kihara D: Enhanced automated function prediction using distantly related sequences and contextual association by PFP. Protein Sci 2006, 15:1550-1556.
• [24]Zhang R, Ou HY, Zhang CT: DEG: a database of essential genes. Nucleic Acids Res 2004, 32(Database issue):D271-D272.
• [25]Moriya Y, Itoh M, Okuda S, Yoshizawa AC, Kanehisa M: KAAS: an automatic genome annotation and pathway reconstruction server. Nucleic Acids Res 2007, 35(Web Server issue):W182-W185.
• [26]Rawlings ND, Barrett AJ: Evolutionary families of peptidases. Biochem J 1993, 290:205-218.
• [27]Cooper JB, Khan G, Taylor G, Tickle IJ, Blundell TL: X-ray analyses of aspartic proteinases. II. Three-dimensional structure of the hexagonal crystal form of porcine pepsin at 2.3 Å resolution. J Mol Biol 1990, 214:199-222.
• [28]Rawlings ND, Morton FR, Kok CY, Kong J, Barrett AJ: MEROPS: the peptidase database. Nucleic Acids Res 2008, 36:D320-D325.
• [29]Sousa NM, Ayad A, Beckers JF, Gajewski Z: Pregnancy associated glycoproteins (PAG) as pregnancy markers in the ruminants. J Phy Pharm 2006, 57(supp 8):153-171.
• [30]Spencer TE, Johnson GA, Bazer FW, Burghardt RC: Implantation mechanisms: insights from the sheep. Reproduction 2004, 128:657-668.
• [31]Ishiwata H, Katsuma S, Kizaki S, Patel OV, Nakano H, Takahashi T, Imai K, Hirasawa A, Shiojima S, Ikawa H, Suzuki Y, Tsujimoto G, Izaike Y, Todoroki J, Hashizume K: Characterization of gene expression profiles in early bovine pregnancy using a custom cDNA microarray. Mol Reprod Dev 2003, 65:9-18.
• [32]Beckers JF, Roberts RM, Zoli AP, Ectors F, Derivaux J: Molecules of the family of aspartic proteinases in the placenta of ruminants: hormones or proteins? Bull Mem Acad R Med Belg 1994, 149:355-367.
• [33]Weems CW, Weems YS, Randel RD: Prostaglandin and reproduction in female farm animals. Vet J 2006, 171:206-228.