A synthetic peptide reproducing the mitochondrial targeting motif of AKAP121: A conformational study(621 views) De Capua A, Del Gatto A, Zaccaro L, Saviano G, Carlucci A, Livigni A, Gedressi C, Tancredi T, Pedone C, Saviano M
Keywords: α-Helix, Akap121, Mitochondrial Targeting (mt) Domain, Synthetic Peptides, Alcohols, Conformations, Data Reduction, Enzyme Kinetics, Mixtures, Molecular Structure, Polypeptides, Motifs, Peptide Reproduction, Trifluoroethanol (tfe), Biopolymers, Cyclic Amp Dependent Protein Kinase, Tubulin, Water, Alpha Helix, Amino Acid Sequence, Amino Terminal Sequence, Circular Dichroism, Conference Paper, Hydrophobicity, Nuclear Magnetic Resonance, Protein Conformation, Protein Domain, Protein Motif, Protein Protein Interaction, Protein Targeting, Structure Analysis, Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, Humans, Models, Molecular Sequence Data, Biomolecular, A Kinase Anchor Proteins, Chemistry, Metabolism, Chemical Synthesis,
Affiliations: *** IBB - CNR ***
Dipartimento di Scienze Ambientali, Seconda Università di Napoli, Caserta, 81100, Italy
Ist. di Biostrutture e Bioimmagini, Dipartimento di Chimica Biologica, Univ. Studi di Napoli Federico II, Napoli, 80134, Italy
Dipto. Sci. e Tecnol. Ambiente e T., Universita degli Studi del Molise, Isernia, 86170, Italy
Dipto. Biol. e Patol. Molec. e Cell., Univ. Studi di Napoli Federico II, Napoli, 80131, Italy
Istituto di Chimica Biomolecolare, CNR, Comprensorio A. Olivetti, via Campki Flegrei 34, Pozzuoli, Napoli, 80078, Italy
References: Edelman, A.M., Blumenthal, D.K., Krebs, E.G., (1987) Annu Rev Biochem, 56, pp. 567-61
Taylor, S.S., Knighton, D.R., Zheng, J., Ten Eyck, L.F., Sowadski, J.M., (1992) Annu Rev Cell Biol, 8, pp. 429-462
Meinkoth, J.L., Alberts, A.S., Went, W., Fantozzi, D., Taylor, S.S., Hagiwara, M., Montminy, M., Feramisco, J.R., (1993) Mol Cell Biochem, 127-128, pp. 179-186
Montminy, M., (1997) Annu Rev Biochem, 66, pp. 807-822
Affaitati, A., Cardone, L., De Crisofaro, T., Carlucci, A., Ginsberg, M.D., Varrone, S., Gottesman, M.E., Feliciello, A., (2003) J Biol Chem, 278, pp. 4286-4294
Harada, H., Becnell, B., Wilm, M., Mann, M., Huang, L.J., Taylor, S.S., Scott, J.D., Korsmeyer, S.J., (1999) Mol Cell, 3, pp. 413-422
Hahne, K., Haucke, V., Ramage, L., Schatz, G., (1994) Cell, 299, pp. 499-520
Rance, M., Sorensen, O.W., Bodenhausen, G., Wagner, G., Ernst, R.R., Wüthrich, K., (1983) Biochem Biophys Res Commun, 117, pp. 479-485
Wüthrich, K., (1986) NMR of Proteins and Nucleic Acids, , Wiley: New York
Bartels, C., Xia, T., Billiter, M., Wüthrich, K., (1995) J Biomol NMR, 5, pp. 1-10
Günter, P., Mumenthaler, C., Wüthrich, K., (1997) J Mol Biol, 273, pp. 283-298
Günter, P., Braun, W., Wüthrieh, K., (1991) J Mol Biol, 217, pp. 517-530
Kim, Y., Prestegard, J.H., (1989) J Magn Reson, 84, pp. 9-13
Simmerling, C.L., Daren, T.A., Merz, K.M., Stanton, R.V., Cheng, A.L., Vincent, J., Crowley, M., Weiner, P.K., (1999) AMBER 6, , University of California, San Francisco
Stewart, J.J.P., (1990) Comput-Aided Mol Design, 4, pp. 1-105
Jakalian, A., Bush, B.L., Jack, D.B., Bayly, C.I., (2000) J Comput Chem, 21, pp. 132-146
Koradi, R., Billeter, M., Wüthrich, K., (1996) J Mol Graphics, 14, pp. 51-55
Sreerama, N., Woody, R.W., (2000) Anal Biochem, 287, pp. 252-260
Rothemund, S., Weisshoff, H., Beyermann, M., Krause, E., Bienert, M., Mugge, C., Sykes, B.D., Sonnichsen, F.D., (1996) J Biomol NMR, 8, pp. 93-97
Pavone, V., Gaeta, G., Lombardi, A., Nastri, F., Maglio, O., Isernia, C., Saviano, M., (1996) Biopolymers, 38, pp. 705-721
Saviano, M., Zaccaro, L., Benedetti, E., Pedone, C., Del Gatto, A., Feliciello, A., Affaiatati, A., Avvedimento, E.V., Peptide Revolution: Genomics, Proteomics & Therapeutics, , Chorev, M., Sawyer, T. K., Eds.
American Peptide Society, 18th American Peptide Symposium, Boston, MA, USA, in press
Edelman, A. M., Blumenthal, D. K., Krebs, E. G., (1987) Annu Rev Biochem, 56, pp. 567-61
Taylor, S. S., Knighton, D. R., Zheng, J., Ten Eyck, L. F., Sowadski, J. M., (1992) Annu Rev Cell Biol, 8, pp. 429-462
Meinkoth, J. L., Alberts, A. S., Went, W., Fantozzi, D., Taylor, S. S., Hagiwara, M., Montminy, M., Feramisco, J. R., (1993) Mol Cell Biochem, 127-128, pp. 179-186
Dell'Acqua, M. L., Scott, J. D., (1997) J Biol Chem, 272, pp. 12881-12884
Edwards, A. S., Scott, J. D., (2000) Curr Opin Cell Biol, 12, pp. 217-221
Rubin, C. S., (1994) Biochim Biophys Acta, 1224, pp. 467-479
Lin, R., Moss, S. B., Rubin, C. S., (1995) J Biol Chem, 270, pp. 27804-27811
Huang, L. J., Durick, K., Weiner, J. A., Chun, J., Taylor, S. S., (1997) J Biol Chem, 272, pp. 8057-8064
Huang, L. J., Wang, L., Ma, Y., Durick, Perkins, G., Deerinck, T. J., Ellisman, M. H., Taylor, S. S., (1999) J Cell Biol, 145, pp. 951-959
Fields, C. G., Lloyd, D. H., Macdonald, R. L., Otteson, K. M., Noble, R. L., (1991) Peptide Res, 4 (2), pp. 95-101
Pace, C. N., Vajdos, F., Fee, L., Grimsley, G., Gray, L., (1995) Protein Sci, 4, pp. 2411-2423
Bax, A., Davis, D. G., (1985) J Magn Res, 65, pp. 355-360
W thrich, K., (1986) NMR of Proteins and Nucleic Acids, , Wiley: New York
G nter, P., Mumenthaler, C., W thrich, K., (1997) J Mol Biol, 273, pp. 283-298
G nter, P., Braun, W., W thrieh, K., (1991) J Mol Biol, 217, pp. 517-530
Simmerling, C. L., Daren, T. A., Merz, K. M., Stanton, R. V., Cheng, A. L., Vincent, J., Crowley, M., Weiner, P. K., (1999) AMBER 6, , University of California, San Francisco
Cornell, W. D., Cieplak, P., Bayly, C. I., Gould, I. R., Merz Jr., K. M., Ferguson, D. M., Spellmeyer, D. C., Kollman, P. A., (1995) J Am Chem Soc, 117, pp. 5179-5197
Stewart, J. J. P., (1990) Comput-Aided Mol Design, 4, pp. 1-105
A synthetic peptide reproducing the mitochondrial targeting motif of AKAP121: A conformational study
The conformational features of a peptide derived by the 10-30 sequence of the mitochondrial domain of AKAP121 [Ac-(1)XKKPLALPGMLALLGWWWFFSRKKX(25)-NH2 (X = beta-Ala)] in water and in a water/triflouroethanol (TFE) mixture at 298 K have been determined by NMR and CD spectroscopy. Backbone clustering analysis of NMR-derived structures led to the identification of a single representative structure in water/TFE. The structure of the peptide consists mainly of an a-helix, whose core is the region 7-23, with a less ordered N-terminal part. These data are confirmed by CD analysis. It is noteworthy that the high hydrophobic Trp(16)-Phe(20) segment, that might also mediate interaction with tubulin, is organized in an a-helical wheel. Our conformational data can be the starting point for the development of highly selective peptides that interfere with the biological function of the Protein Kinase A scaffold protein AKAP121. (C) 2004 Wiley Periodicals, Inc.
A synthetic peptide reproducing the mitochondrial targeting motif of AKAP121: A conformational study