Keywords: Cd Spectroscopy, Domain Refolding, Enzyme Digestion, Peptide Synthesis, Receptor Binding, Growth Factor, Protein Cripto, Unclassified Drug, Article, Circular Dichroism, Conformational Transition, Molecular Recognition, Mouse, Nonhuman, Priority Journal, Protein Domain, Protein Synthesis, Activin Receptors, Type I, Amino Acid Sequence, Animals, Binding Sites, Chromatography, Liquid, Epidermal Growth Factor, Kinetics, Mass Spectrometry, Membrane Glycoproteins, Models, Molecular Sequence Data, Mutation, Neoplasm Proteins, Protein Binding, Protein Folding, Protein Structure, Tertiary, Recombinant Proteins, Sequence Homology,
Affiliations: *** IBB - CNR ***
Istituto di Biostrutture e Bioimmagini del CNR, Sezione Biostrutture, Napoli, Italy
Istituto di Genetica e Biofisica Adriano B. Traverso del CNR, Napoli, Italy
Facoltà di Scienze MMFFNN, Seconda Università di Napoli, Caserta, Italy
Facolt di Scienze MMFFNN, Seconda Universit di Napoli, Caserta, Italy
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Adamson, E. D., Minchiotti, G., Salomon, D. S., Cripto: A tumor growth factor and more (2002) J Cell Biol, 190, pp. 267-278
Salomon, D. S., Bianco, C., Ebert, A. D., The EGF-CFC family: Novel epidermal growth factor-related proteins in development and cancer (2000) Endocr Relat Cancer, 7, pp. 199-226
Foley, S. F., Van Vlijmen, H. W., Boynton, R. E., The CRIPTO/FRL-1/CRYPTIC (CFC) domain of human Cripto. Functional and structural insights through disulfide structure analysis (2003) Eur J Biochem, 270, pp. 3610-3618
Yeo, C. Y., Whitman, M., Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms (2001) Mol Cell, 7, pp. 949-957
Shen, M. M., Schier, A. F., The EGF-CFC gene family in vertebrate development (2000) Trends Genet, 16, pp. 303-309
Xing, P. X., Hu, X. F., Pietersz, G. A., Hosick, H. L., McKenzie, I. F. C., Cripto: A novel target for antibody-based cancer immunotherapy (2004) Cancer Res, 64, pp. 4018-4023
Herrington, E. E., Ram, T. G., Salomon, D. S., Expression of epidermal growth factor-related proteins in the aged adult mouse mammary gland and their relationship to tumorigenesis (1997) J Cell Physiol, 170, pp. 47-56
Kenney, N. J., Smith, G. H., Maroulakou, I. G., Detection of amphiregulin and Cripto-1 in mammary tumors from transgenic mice (1996) Mol Carcinog, 15, pp. 44-56
Adkins, H. B., Bianco, C., Schiffer, S. G., Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo (2003) J Clin Invest, 112, pp. 575-587
Gray, P. C., Harrison, C. A., Vale, W., Cripto forms a complex with activin and type II activin receptors and can block activin signaling (2003) Proc Natl Acad Sci USA, 100, pp. 5193-5198
Persico, M. G., Liguori, G. L., Parisi, S., D'Andrea, D., Salomon, D. S., Minchiotti, G., Cripto in tumors and embryo development (2001) Biochim Biophys Acta, 1552, pp. 87-93
Song, J., Oh, S. P., Schrewe, H., The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice (1999) Dev Biol, 213, pp. 157-169
Schier, A. F., Shen, M. M., Nodal signalling in vertebrate development (2000) Nature, 403, pp. 385-389
Schiffer, S. G., Foley, S., Kaffashan, A., Fucosylation of Cripto is required for its ability to facilitate nodal signaling (2001) J Biol Chem, 276, pp. 37769-37778
Barcellos-Hoff, M. H., Ewan, K. B., Transforming growth factor-beta and breast cancer: Mammary gland development (2000) Breast Cancer Res, 2, pp. 92-99
Risbridger, G. P., Schmitt, J. F., Robertson, D. M., Activins and inhibins in endocrine and other tumors (2001) Endocr Rev, 22, pp. 836-858
Wakefield, L. M., Roberts, A. B., TGF-beta signaling: Positive and negative effects on tumorigenesis (2002) Curr Opin Genet Dev, 12, pp. 22-29
Harrison, C. A., Gray, P. C., Vale, W. W., Robertson, D. M., Antagonists of activin signaling: Mechanisms and potential biological applications (2005) Trends Endocrinol Metab, 16, pp. 73-78
Cheng, S. K., Olale, F., Bennett, J. T., Brivanlou, A. H., Schier, A. F., EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1 (2003) Gene Dev, 17, pp. 31-36
Johnson Jr., W. C., Protein secondary structure and circular dichroism: A practical guide (1990) Proteins, 7, pp. 205-214
Fields, G. B., Noble, R. L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxy-carbonil amino acids (1990) Int J Pept Protein Res, 35, pp. 161-214
Tam, J. P., Wu, C. R., Liu, W., Zhang, J. W., Bisulfide bond formation in peptides by dimethyl sulfoxide. Scope and applications (1991) J Am Chem Soc, 113, pp. 6657-6662
Moroney, J. V., Fullmer, C. S., McCarty, R. E., Characterization of the cysteinyl-containing peptides of the gamma subunit of coupling factor 1 (1984) J Biol Chem, 259, pp. 7281-7285
Chemical synthesis of mouse Cripto CFC variants
We report for the first time the chemical synthesis of refolded CFC domain of mouse Cripto (mCFC) and of two variants bearing mutations on residues W107 and H104 involved in Alk4 binding. The domains undergo spontaneous and quantitative refolding in about 4 h, yet with very different kinetics. Disulfide linkages have been assessed by enzyme digestion and mass spectrometry analysis of resulting fragments, and the first experimental studies on structural organization have been conducted by circular dichroism spectroscopy under different pH conditions. Upon refolding, the domains considerably change their conformations, although they do not assume canonical structures, and become highly resistant to enzyme degradation. A comparative study of receptor binding shows that the CFC domain can bind Alk4 and confirms the importance of W107 and H104 for receptor recognition.
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(449 views) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 ViewExport to BibTeXExport to EndNote