Conformational features and binding affinities to Cripto, ALK7 and ALK4 of Nodal synthetic fragments(496 views) Calvanese L, Sandomenico A, Caporale A, Foca A, Foca G, D'Auria G, Falcigno L, Ruvo M
Keywords: Nmr, Peptides, Nodal, Tgf-Beta, Alanine Derivative, Cripto Membrane Protein, Epitope, Glutamic Acid, Peptide Fragment, Protein Nodal, Protein Serine Threonine Kinase, Protein Serine Threonine Kinase Alk4, Recombinant Protein, Synthetic Peptide, Unclassified Drug, Article, Binding Affinity, Carboxy Terminal Sequence, Circular Dichroism, Complex Formation, Human, In Vitro Study, Molecular Docking, Molecular Model, Nuclear Overhauser Effect, Priority Journal, Protein Analysis, Protein Conformation, Protein Function, Protein Interaction, Protein Structure, Proton Nuclear Magnetic Resonance, Signal Transduction, Static Electricity, Surface Plasmon Resonance, Wild Type,
Affiliations: *** IBB - CNR ***
CIRPeB University of Naples Federico II via Mezzocannone, 16 80134 Napoli Italy
Istituto di Biostrutture e Bioimmagini del CNR via Mezzocannone 16, 80134 Napoli Italy
Dipartimento di Farmacia University of Naples Federico II via Mezzocannone, 16 80134 Napoli Italy
Bioker Multimedica via P. Castellino Napoli 111 Italy
CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134, Napoli, Italy.
Bioker Multimedica, via P. Castellino, Napoli, Italy
1CIRPeB, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy
2CNR-IBB, via Mezzocannone, 16, 80134 Napoli, Italy
3Dept. of Pharmacy, University of Naples Federico II, via Mezzocannone, 16, 80134 Napoli, Italy. 4Bioker Multimedica, via P. Castellino, 111, Napoli, Italy.
References: Jornvall, H., Reissmann, E., Andersson, O., Mehrkash, M., Ibanez, C.F., ALK7, a receptor for nodal, is dispensable for embryogenesis and left-right patterning in the mouse (2004) Mol. Cell. Biol., 24, pp. 9383-938
James, D., Levine, A.J., Besser, D., Hemmati-Brivanlou, A., TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells (2005) Development, 132, pp. 1273-1282
Pantic, I., Cancer stem cell hypotheses: Impact on modern molecular physiology and pharmacology research (2011) J. Biosci., 36, pp. 957-961
Quail, D.F., Siegers, G.M., Jewer, M., Postovit, L.M., Nodal signalling in embryogenesis and tumourigenesis (2013) Int. J. Biochem. Cell Biol., 45, pp. 885-898
Xu, G., Zhong, Y., Munir, S., Yang, B.B., Tsang, B.K., Peng, C., Nodal induces apoptosis and inhibits proliferation in human epithelial ovarian cancer cells via activin receptor-like kinase 7 (2004) J. Clin. Endocrinol. Metab., 89, pp. 5523-5534
Hermann, P.C., Huber, S.L., Herrler, T., Aicher, A., Ellwart, J.W., Guba, M., Bruns, C.J., Heeschen, C., Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer (2007) Cell Stem Cell, 1, pp. 313-323
Lonardo, E., Hermann, P.C., Mueller, M.T., Huber, S., Balic, A., Miranda-Lorenzo, I., Zagorac, S., Heeschen, C., Nodal/activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy (2011) Cell Stem Cell, 9, pp. 433-446
Papageorgiou, I., Nicholls, P.K., Wang, F., Lackmann, M., Makanji, Y., Salamonsen, L.A., Robertson, D.M., Harrison, C.A., Expression of nodal signalling components in cycling human endometrium and in endometrial cancer (2009) Reproductive Biol. Endocrinol.: RB&E, 7, p. 122
Quail, D.F., Walsh, L.A., Zhang, G., Findlay, S.D., Moreno, J., Fung, L., Ablack, A., Postovit, L.M., Embryonic protein nodal promotes breast cancer vascularization (2012) Cancer Res., 72, pp. 3851-3863
Strizzi, L., Hardy, K.M., Margaryan, N.V., Hillman, D.W., Seftor, E.A., Chen, B., Geiger, X.J., Hendrix, M.J., Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer (2012) Breast Canc. Res.: BCR, 14, p. R75
Kirsammer, G., Strizzi, L., Margaryan, N.V., Gilgur, A., Hyser, M., Atkinson, J., Kirschmann, D.A., Hendrix, M.J., Nodal signaling promotes a tumorigenic phenotype in human breast cancer (2014) Semin. Cancer Biol.
Vo, B.T., Cody, B., Cao, Y., Khan, S.A., Differential role of Sloan-Kettering Institute (Ski) protein in Nodal and transforming growth factor-beta (TGF-beta)-induced Smad signaling in prostate cancer cells (2012) Carcinogenesis, 33, pp. 2054-2064
Lawrence, M.G., Margaryan, N.V., Loessner, D., Collins, A., Kerr, K.M., Turner, M., Seftor, E.A., Hendrix, M.J., Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells (2011) Prostate, 71, pp. 1198-1209
Spiller, C.M., Bowles, J., Koopman, P., Nodal/Cripto signaling in fetal male germ cell development: Implications for testicular germ cell tumors (2013) Int. J. Dev. Biol., 57, pp. 211-219
Lee, C.C., Jan, H.J., Lai, J.H., Ma, H.I., Hueng, D.Y., Lee, Y.C., Cheng, Y.Y., Lee, H.M., Nodal promotes growth and invasion in human gliomas (2010) Oncogene, 29, pp. 3110-3123
Tysnes, B.B., Satran, H.A., Mork, S.J., Margaryan, N.V., Eide, G.E., Petersen, K., Strizzi, L., Hendrix, M.J., Age-dependent association between protein expression of the embryonic stem cell marker Cripto-1 and survival of glioblastoma patients (2013) Translational Oncology, 6, pp. 732-741
Gong, Y., Yu, T., Chen, B., He, M., Li, Y., Removal of cardiopulmonary resuscitation artifacts with an enhanced adaptive filtering method: An experimental trial (2014) BioMed Res. Int., 2014, p. 140438
Seftor, E.A., Seftor, R.E., Weldon, D.S., Kirsammer, G.T., Margaryan, N.V., Gilgur, A., Hendrix, M.J., Melanoma tumor cell heterogeneity: A molecular approach to study subpopulations expressing the embryonic morphogen nodal (2014) Semin. Oncol., 41, pp. 259-266
Topczewska, J.M., Postovit, L.M., Margaryan, N.V., Sam, A., Hess, A.R., Wheaton, W.W., Nickoloff, B.J., Hendrix, M.J., Embryonic and tumorigenic pathways converge via Nodal signaling: Role in melanoma aggressiveness (2006) Nat. Med., 12, pp. 925-932
Chen, J., Liu, W.B., Jia, W.D., Xu, G.L., Ma, J.L., Ren, Y., Chen, H., Li, J.S., Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma (2014) PLoS One, 9, p. e85840
Ganapathy, V., Ge, R., Grazioli, A., Xie, W., Banach-Petrosky, W., Kang, Y., Lonning, S., Reiss, M., Targeting the transforming growth factor-beta pathway inhibits human basal-like breast cancer metastasis (2010) Mol. Cancer, 9, p. 122
Korpal, M., Kang, Y., Targeting the transforming growth factor-beta signalling pathway in metastatic cancer (2010) Eur. J. Cancer, 46, pp. 1232-1240
Wakefield, L.M., Hill, C.S., Beyond TGFbeta: Roles of other TGFbeta superfamily members in cancer (2013) Nat. Rev. Cancer, 13, pp. 328-341
Reissmann, E., Jornvall, H., Blokzijl, A., Andersson, O., Chang, C., Minchiotti, G., Persico, M.G., Brivanlou, A.H., The orphan receptor ALK7 and the activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development (2001) Genes Dev., 15, pp. 2010-2022
Schier, A.F., Shen, M.M., Nodal signalling in vertebrate development (2000) Nature, 403, pp. 385-389
Yeo, C., Whitman, M., Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms (2001) Mol. Cell, 7, pp. 949-957
Minchiotti, G., Manco, G., Parisi, S., Lago, C.T., Rosa, F., Persico, M.G., Structure-function analysis of the EGF-CFC family member Cripto identifies residues essential for nodal signalling (2001) Development, 128, pp. 4501-4510
Khalkhali-Ellis, Z., Kirschmann, D.A., Seftor, E.A., Gilgur, A., Bodenstine, T.M., Hinck, A.P., Hendrix, M.J., Divergence(s) in nodal signaling between aggressive melanoma and embryonic stem cells (2014) Int. J. Canc. J. Int. du Canc.
Calvanese, L., Marasco, D., Doti, N., Saporito, A., D'Auria, G., Paolillo, L., Ruvo, M., Falcigno, L., Structural investigations on the Nodal-Cripto binding: A theoretical and experimental approach (2010) Biopolymers, 93, pp. 1011-1021
Romano, V., Raimondo, D., Calvanese, L., D'Auria, G., Tramontano, A., Falcigno, L., Toward a better understanding of the interaction between TGF-beta family members and their ALK receptors (2012) J. Mol. Model., 18, pp. 3617-3625
Lin, S.J., Lerch, T.F., Cook, R.W., Jardetzky, T.S., Woodruff, T.K., The structural basis of TGF-beta, bone morphogenetic protein, and activin ligand binding (2006) Reproduction, 132, pp. 179-190
Greenwald, J., Vega, M.E., Allendorph, G.P., Fischer, W.H., Vale, W., Choe, S., A flexible activin explains the membrane-dependent cooperative assembly of TGF-beta family receptors (2004) Mol. Cell, 15, pp. 485-489
Muenster, U., Korupolu, R., Rastogi, R., Read, J., Fischer, W.H., Antagonism of activin by activin chimeras (2011) Vitam. Horm., 85, pp. 105-128
Thompson, T.B., Woodruff, T.K., Jardetzky, T.S., Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions (2003) Embo. J., 22, pp. 1555-1566
Fields, G.B., Noble, R.L., Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids (1990) Int. J. Pept. Protein Res., 35, pp. 161-214
Bax, A., Davis, D.G., MLEV-17-based two-dimensional homonuclear magnetization transfer spectroscopy (1985) J. Magn. Res., 65, pp. 355-360
States, D., Haberhorn, R., Ruben, D., A two-dimensional nuclear Overhauser experiment with pure absorption phase in four quadrants (1982) J. Magn. Res., 48, pp. 286-292
Delaglio, F., Grzesiek, S., Vuister, G.W., Zhu, G., Pfeifer, J., Bax, A., NMRPipe: A multidimensional spectral processing system based on UNIX pipes (1995) J. Biomol. NMR, 6, pp. 277-293
Johnson, B.A., Using NMRView to visualize and analyze the NMR spectra of macromolecules (2004) Methods Mol. Biol., 278, pp. 313-352
Guntert, P., Braun, W., Wuthrich, K., Efficient computation of three-dimensional protein structures in solution from nuclear magnetic resonance data using the program DIANA and the supporting programs CALIBA, HABAS and GLOMSA (1991) J. Mol. Biol., 217, pp. 517-530
Guntert, P., Mumenthaler, C., Wuthrich, K., Torsion angle dynamics for NMR structure calculation with the new program DYANA (1997) J. Mol. Biol., 273, pp. 283-298
Guntert, P., Automated NMR structure calculation with CYANA (2004) Methods Mol. Biol., 278, pp. 353-378
Pearlman, D.A., Case, D.A., Caldwell, J.W., Ross, W.S., Cheatham Iii., T.E., Debolt, S., Ferguson, D., Kollman, P., AMBER, a package of computer program for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules (1995) Comp. Phys. Commun., 91, pp. 1-41
Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E., UCSF Chimera-A visualization system for exploratory research and analysis (2004) J. Comput. Chem., 25, pp. 1605-1612
Koradi, R., Billeter, M., Wuthrich, K., MOLMOL: A program for display and analysis of macromolecular structures (1996) J. Mol. Graph., 14, pp. 51-55. , 29-32
Wuthrich, K., (1986) NMR of Proteins and Nucleic Acids, , Wiley: New York
Wishart, D.S., Sykes, B.D., Richards, F.M., Relationship between nuclear magnetic resonance chemical shift and protein secondary structure (1991) J. Mol. Biol., 222, pp. 311-333
Conformational features and binding affinities to Cripto, ALK7 and ALK4 of Nodal synthetic fragments
Nodal, a member of the TGF-beta superfamily, is a potent embryonic morphogen also implicated in tumor progression. As for other TGF-betas, it triggers the signaling functions through the interaction with the extracellular domains of type I and type II serine/threonine kinase receptors and with the co-receptor Cripto. Recently, we reported the molecular models of Nodal in complex with its type I receptors (ALK4 and ALK7) as well as with Cripto, as obtained by homology modeling and docking simulations. From such models, potential binding epitopes have been identified. To validate such hypotheses, a series of mutated Nodal fragments have been synthesized. These peptide analogs encompass residues 44-67 of the Nodal protein, corresponding to the pre-helix loop and the H3 helix, and reproduce the wild-type sequence or bear some modifications to evaluate the hot-spot role of modified residues in the receptor binding. Here, we show the structural characterization in solution by CD and NMR of the Nodal peptides and the measurement of binding affinity toward Cripto by surface plasmon resonance. Data collected by both conformational analyses and binding measurements suggest a role for Y58 of Nodal in the recognition with Cripto and confirm that previously reported for E49 and E50. Surface plasmon resonance binding assays with recombinant proteins show that Nodal interacts in vitro also with ALK7 and ALK4 and preliminary data, generated using the Nodal synthetic fragments, suggest that Y58 of Nodal may also be involved in the recognition with these protein partners. Copyright (c) 2015 European Peptide Society and John Wiley & Sons, Ltd
Conformational features and binding affinities to Cripto, ALK7 and ALK4 of Nodal synthetic fragments
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Conformational features and binding affinities to Cripto, ALK7 and ALK4 of Nodal synthetic fragments