Abstract
Ca2+ plays a pivotal role in the physiology and biochemistry of prokaryotic and mammalian organisms. Viruses also utilize the universal Ca2+ signal to create a specific cellular environment to achieve coexistence with the host, and to propagate. In this paper we first describe our development of a grafting approach to understand site-specific Ca2+ binding properties of EF-hand proteins with a helix-loop-helix Ca2+ binding motif, then summarize our prediction and identification of EF-hand Ca2+ binding sites on a genome-wide scale in bacteria and virus, and next report the application of the grafting approach to probe the metal binding capability of predicted EF-hand motifs within the streptococcal hemoprotein receptor (Shr) of Streptococcus pyrogenes and the nonstructural protein 1 (nsP1) of Sindbis virus. When methods such as the grafting approach are developed in conjunction with prediction algorithms we are better able to probe continuous Ca2+-binding sites that have been previously underrepresented due to the limitation of conventional methodology.
Keywords: Ca2+, EF-hand calcium binding pockets, protein grafting approach, Streptococcus pyrogenes, Sindbis virus
References
- 1.Berridge M.J., Bootman M.D., Lipp P. Calcium: a life and death signal. Nature. 1998;395:645–648. doi: 10.1038/27094. [DOI] [PubMed] [Google Scholar]
- 2.Verkhratsky A. Calcium and cell death. Subcell Biochem. 2007;45:465–480. doi: 10.1007/978-1-4020-6191-2_17. [DOI] [PubMed] [Google Scholar]
- 3.Berridge M.J., Bootman M.D., Roderick H.L. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 2003;4:517–529. doi: 10.1038/nrm1155. [DOI] [PubMed] [Google Scholar]
- 4.Nayler W.G. Calcium and cell death. Eur Heart J. 1983;4(SupplC):33–41. doi: 10.1093/eurheartj/4.suppl_c.33. [DOI] [PubMed] [Google Scholar]
- 5.Wankerl M., Schwartz K. Calcium transport proteins in the nonfailing and failing heart: gene expression and function. J Mol Med. 1995;73:487–496. doi: 10.1007/BF00198900. [DOI] [PubMed] [Google Scholar]
- 6.Zhou Y., Frey T.K., Yang J.J. Viral calciomics: interplays between Ca2+ and virus. Cell Calcium. 2009;46:1–17. doi: 10.1016/j.ceca.2009.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Zhao L., Liu Y., Bruzik K.S., Tsai M.D. A novel calcium-dependent bacterial phosphatidylinositol-specific phospholipase C displaying unprecedented magnitudes of thio effect, inverse thio effect, and stereoselectivity. J Am Chem Soc. 2003;125:22–23. doi: 10.1021/ja029019n. [DOI] [PubMed] [Google Scholar]
- 8.Gangola P., Rosen B.P. Maintenance of intracellular calcium in Escherichia coli. J Biol Chem. 1987;262:12570–12574. [PubMed] [Google Scholar]
- 9.Tsujibo H., Rosen B.P. Energetics of calcium efflux from cells of Escherichia coli. J Bacteriol. 1983;154:854–858. doi: 10.1128/jb.154.2.854-858.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Watkins N.J., Knight M.R., Trewavas A.J., Campbell A.K. Free calcium transients in chemotactic and non-chemotactic strains of Escherichia coli determined by using recombinant aequorin. Biochem J. 1995;306:865–869. doi: 10.1042/bj3060865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Reusch R.N., Huang R., Bramble L.L. Poly-3-hydroxybutyrate/polyphosphate complexes form voltage-activated Ca2+ channels in the plasma membranes of Escherichia coli. Biophys J. 1995;69:754–766. doi: 10.1016/S0006-3495(95)79958-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Trombe M.C. Characterization of a calcium porter of Streptococcus pneumoniae involved in calcium regulation of growth and competence. J Gen Microbiol. 1993;139:433–439. doi: 10.1099/00221287-139-3-433. [DOI] [PubMed] [Google Scholar]
- 13.Trombe M.C., Rieux V., Baille F. Mutations which alter the kinetics of calcium transport alter the regulation of competence in Streptococcus pneumoniae. J Bacteriol. 1994;176:1992–1996. doi: 10.1128/jb.176.7.1992-1996.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Hauck C.R. Cell adhesion receptors: signaling capacity and exploitation by bacterial pathogens. Med Microbiol Immunol (Berl) 2002;191:55–62. doi: 10.1007/s00430-002-0119-0. [DOI] [PubMed] [Google Scholar]
- 15.Norris V., Chen M., Goldberg M., Voskuil J., McGurk G., Holland I.B. Calcium in bacteria: a solution to which problem? Mol Microbiol. 1991;5:775–778. doi: 10.1111/j.1365-2958.1991.tb00748.x. [DOI] [PubMed] [Google Scholar]
- 16.Norris V., Grant S., Freestone P., Canvin J., Sheikh F. N., Toth I., Trinei M., Modha K., Norman R. I. Calcium signalling in bacteria. J Bacteriol. 1996;178:3677–3682. doi: 10.1128/jb.178.13.3677-3682.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Rigden D.J., Jedrzejas M.J., Galperin M.Y. An extracellular calcium-binding domain in bacteria with a distant relationship to EFhands. FEMS Microbiol Lett. 2003;221:103–110. doi: 10.1016/S0378-1097(03)00160-5. [DOI] [PubMed] [Google Scholar]
- 18.Kawasaki H., Nakayama S., Kretsinger R.H. Classification and evolution of EF-hand proteins. Biometals. 1998;11:277–295. doi: 10.1023/A:1009282307967. [DOI] [PubMed] [Google Scholar]
- 19.Kim Y., Welch J.T., Lindstrom K.M., Franklin S.J. Chimeric HTH motifs based on EF-hands. J Biol Inorg Chem. 2001;6:173–181. doi: 10.1007/s007750000188. [DOI] [PubMed] [Google Scholar]
- 20.Pal G.P., Elce J.S., Jia Z. Dissociation and aggregation of calpain in the presence of calcium. J Biol Chem. 2001;276:47233–47238. doi: 10.1074/jbc.M105149200. [DOI] [PubMed] [Google Scholar]
- 21.Raser K.J., Buroker-Kilgore M., Wang K.K. Binding and aggregation of human mu-calpain by terbium ion. Biochim Biophys Acta. 1996;1292:9–14. doi: 10.1016/0167-4838(95)00170-0. [DOI] [PubMed] [Google Scholar]
- 22.Ravulapalli R., Diaz B.G., Campbell R. L., Davies P. L. Homodimerization of calpain 3 penta-EF-hand domain. Biochem J. 2005;388:585–591. doi: 10.1042/BJ20041821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Ye Y., Lee H.W., Yang W., Shealy S., Yang J.J. Probing site-specific calmodulin calcium and lanthanide affinity by grafting. J Am Chem Soc. 2005;127:3743–3750. doi: 10.1021/ja042786x. [DOI] [PubMed] [Google Scholar]
- 24.Chen G., Deng H., Yang W., Yang J.J. Predicting calcium binding sites in proteins-a graph theory and geometry approach. Proteins. 2006;64(1):34–42. doi: 10.1002/prot.20972. [DOI] [PubMed] [Google Scholar]
- 25.Ye Y., Lee H. W., Yang W., Yang J. J. Calcium and lanthanide affinity of the EF-loops from the C-terminal domain of calmodulin. J Inorg Biochem. 2005;99:1376–1383. doi: 10.1016/j.jinorgbio.2005.03.011. [DOI] [PubMed] [Google Scholar]
- 26.Yang W., Wilkins A. L., Ye Y., Liu Z.R., Li S.Y., Urbauer J.L., Hellinga H.W., Kearney A., van der Merwe P.A., Yang J.J. Design of a calcium-binding protein with desired structure in a cell adhesion molecule. J Am Chem Soc. 2005;127:2085–2093. doi: 10.1021/ja0431307. [DOI] [PubMed] [Google Scholar]
- 27.Yang W., Wilkins A.L., Li S., Ye Y., Yang J.J. The effects of ca2+ binding on the dynamic properties of a designed ca2+-binding protein(,) Biochemistry. 2005;44:8267–8273. doi: 10.1021/bi050463n. [DOI] [PubMed] [Google Scholar]
- 28.Yang J.J., Yang W. In: The Encyclopedia of Inorganic Chemistry, Second Edition. King R. B., editor. West Sussex UK: John Wiley & Sons, Ltd.; 2005. pp. 227–282. [Google Scholar]
- 29.Ye Y., Shealy S., Lee H.W., Torshin I., Harrison R., Yang J.J. A grafting approach to obtain site-specific metal-binding properties of EF-hand proteins. Protein Eng. 2003;16:429–434. doi: 10.1093/protein/gzg051. [DOI] [PubMed] [Google Scholar]
- 30.Yang W., Jones L.M., Isley L., Ye Y., Lee H.W., Wilkins A., Liu Z.R., Hellinga H.W., Malchow R., Ghazi M., Yang J.J. Rational design of a calcium-binding protein. J Am Chem Soc. 2003;125:6165–6171. doi: 10.1021/ja034724x. [DOI] [PubMed] [Google Scholar]
- 31.Yang J.J., Gawthrop A., Ye Y. Obtaining site-specific calcium-binding affinities of calmodulin. Protein Pept Lett. 2003;10:331–345. doi: 10.2174/0929866033478852. [DOI] [PubMed] [Google Scholar]
- 32.Yang W., Lee H.W., Hellinga H., Yang J.J. Structural analysis, identification, and design of calcium-binding sites in proteins. Proteins. 2002;47:344–356. doi: 10.1002/prot.10093. [DOI] [PubMed] [Google Scholar]
- 33.Wilkins A.L., Ye Y., Yang W., Lee H.W., Liu Z.R., Yang J.J. Metalbinding studies for a de novo designed calcium-binding protein. Protein Eng. 2002;15:571–574. doi: 10.1093/protein/15.7.571. [DOI] [PubMed] [Google Scholar]
- 34.Lee H.W., Yang W., Ye Y., Liu Z.R., Glushka J., Yang J.J. Isolated EF-loop III of calmodulin in a scaffold protein remains unpaired in solution using pulsed-field-gradient NMR spectroscopy. Biochim Biophys Acta. 2002;1598:80–87. doi: 10.1016/s0167-4838(02)00338-2. [DOI] [PubMed] [Google Scholar]
- 35.Ellis A. L., Mason J.C., Lee H.W., Strekowski L., Patonay G., Choi H., Yang J.J. Design, synthesis, and characterization of a calcium-sensitive near infrared dye. Talanta. 2002;56:1099–1107. doi: 10.1016/S0039-9140(01)00641-5. [DOI] [PubMed] [Google Scholar]
- 36.Ye Y, Yang JJ. Calcium binding properties of EF-loops in a beta-sheet protein. Escom Leiden, 2001
- 37.Ye Y., Lee H.W., Yang W., Shealy S.J., Wilkins A.L., Liu Z.R., Torshin I., Harrison R., Wohlhueter R., Yang J.J. Metal binding affinity and structural properties of an isolated EF-loop in a scaffold protein. Protein Eng. 2001;14:1001–1013. doi: 10.1093/protein/14.12.1001. [DOI] [PubMed] [Google Scholar]
- 38.Yang W., Lee H., Liu Z., Hellinga H.W., Yang J.J. Criteria for Designing a Calcium Binding Protein. Norwell: Kluwer; 2001. [Google Scholar]
- 39.Yang W., Tsai T., Kats M., Yang J.J. Peptide analogs from E-cadherin with different calcium-binding affinities. J Pept Res. 2000;55:203–215. doi: 10.1034/j.1399-3011.2000.00169.x. [DOI] [PubMed] [Google Scholar]
- 40.Yang W, Lee HW, Pu M, Hellinga H, Yang JJ. Identifying and designing of calcium binding sites in proteins by computational algorithm. In: Computational Studies, Nanotechnology, and Solution Thermodynamics of Polymer Systems. Kluwer Academic/Plenum Publishers, 2000. 127–138
- 41.Zhou Y., Yang W., Kirberger M., Lee H.W., Ayalasomayajula G., Yang J.J. Prediction of EF-hand calcium-binding proteins and analysis of bacterial EF-hand proteins. Proteins. 2006;65:643–655. doi: 10.1002/prot.21139. [DOI] [PubMed] [Google Scholar]
- 42.Herbaud M.L., Guiseppi A., Denizot F., Haiech J., Kilhoffer M.C. Calcium signalling in Bacillus subtilis. Biochim Biophys Acta. 1998;1448:212–226. doi: 10.1016/S0167-4889(98)00145-1. [DOI] [PubMed] [Google Scholar]
- 43.Gangola P., Rosen B.P. Maintenance of intracellular calcium in Escherichia coli. J Biol Chem. 1987;262:12570–12574. [PubMed] [Google Scholar]
- 44.Aitio H., Annila A., Heikkinen S., Thulin E., Drakenberg T., Kilpelainen I. NMR assignments, secondary structure, and global fold of calerythrin, an EF-hand calcium-binding protein from Saccharopolyspora erythraea. Protein Sci. 1999;8:2580–2588. doi: 10.1110/ps.8.12.2580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Aitio H., Annila A., Heikkinen S., Thulin E., Drakenberg T., Kilpelainen I. NMR assignments, secondary structure, and global fold of calerythrin, an EF-hand calcium-binding protein from Saccharopolyspora erythraea. Protein Sci. 1999;8:2580–2588. doi: 10.1110/ps.8.12.2580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Vyas N.K., Vyas M.N., Quiocho F.A. A novel calcium binding site in the galactose-binding protein of bacterial transport and chemotaxis. Nature. 1987;327:635–638. doi: 10.1038/327635a0. [DOI] [PubMed] [Google Scholar]
- 47.Carvalho A.L., Dias F.M., Prates J.A., Nagy T., Gilbert H.J., Davies G.J., Ferreira L.M., Romao M.J., Fontes C.M. Cellulosome assembly revealed by the crystal structure of the cohesin-dockerin complex. Proc Natl Acad Sci USA. 2003;100:13809–13814. doi: 10.1073/pnas.1936124100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Lin J., Ficht T.A. Protein synthesis in Brucella abortus induced during macrophage infection. Infect Immun. 1995;63:1409–1414. doi: 10.1128/iai.63.4.1409-1414.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Teixeira-Gomes A.P., Cloeckaert A., Zygmunt M.S. Characterization of heat, oxidative, and acid stress responses in Brucella melitensis. Infect Immun. 2000;68:2954–2961. doi: 10.1128/IAI.68.5.2954-2961.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Andrade M.A., Ciccarelli F.D., Perez-Iratxeta C., Bork P. NEAT: a domain duplicated in genes near the components of a putative Fe3+ siderophore transporter from Gram-positive pathogenic bacteria. Genome Biol. 2002;3:RESEARCH0047. doi: 10.1186/gb-2002-3-9-research0047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Zhou Y., Tzeng W.P., Yang W., Zhou Y., Ye Y., Lee H.W., Frey T.K., Yang J. Identification of a Ca2+-binding domain in the rubella virus nonstructural protease. J Virol. 2007;81:7517–7528. doi: 10.1128/JVI.00605-07. [DOI] [PMC free article] [PubMed] [Google Scholar]