Abstract
The sequences of nine different cytokines, growth hormone, and prolactin have been aligned and their secondary structure predicted. The alignment reveals that each exon has a characteristic sequence pattern shared by all cytokines. The most striking sequence similarity is observed in exon 4, where the residue pair Phe-Leu is conserved in many cytokines. In addition, there are discreet homologous regions between two specific growth factors, including a high degree of homology between granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3). The secondary structure analysis predicts that exon 3 of all cytokines has an antiparallel helix-turn-helix motif, which is likely to form the central helical segments of a four α-helical bundle-type structure. Based on the secondary structure and the disulfidebonding pattern, the topological connectivity for a number of cytokines has been predicted.
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Abdel-Meguid, S. S., Shieh, H.-S., Smith, W. W., Dayringer, H. E., Violand, B. N., and Bentle, L. A. (1987).Proc. Natl. Acad. Sci. USA 84, 6434–6437.
Arai, K.-I., Lee, F., Miyajima, A., Miyatake, S., Arai, N., and Yokota, T. (1990).Annu. Rev. Biochem. 59, 783–836.
Azuma, C., Tanabe, T., Konishi, M., Kinashi, T., Noma, T., Matsuda, F., Yaoita, Y., Takatsu, K., Hammarstrom, L., Smith, C. I. E., Severinson, E., and Honjo, T. (1986).Nucl. Acids Res. 14, 9149–9158.
Barta, A., Richards, R., Baxter, J. D., and Shine, J. (1981).Proc. Natl. Acad. Sci. USA 78, 4853–4871.
Baxan, J. F. (1990).Immunol. Today 11, 350–354.
Bazan, J. F. (1989).Biochem. Biophys. Res. Comm. 164, 788.
Brandhuber, B. J., Boone, T., Kenney, W. C., and McKay, D. B. (1987).Science 238, 1707–1709.
Carr, C., Aykent, S., Kimack, N. M., and Levine, A. D. (1991).Biochemistry 30, 1515–1523.
Chou, P.-Y., and Fasman, G. D. (1978).Annu. Rev. Biochem. 47, 251–276.
Chou, K.-C., Maggiora, G. M., Nemethy, G., and Scheraga, H. A. (1988).Proc. Natl. Acad. Sci. USA 85, 4295–4299.
Clark-Lewis, I., Lopez, A. F., Vadas, M., Schrader, J. W., Hood, L. E., and Kent, S. B. H. (1987). InMolecular Basis for Lymphokine Action (Webb, D., Pierce, C., and Cohen, S.), Humana, Clifton, New Jersey, pp. 339–351.
Cohen, F. E., Abarbanel, R. M., Kuntz, I. D., and Fletterick, R. J. (1986).Biochemistry 25, 266–275.
Cooke, N. E., Coit, D., Shine, J., Baxter, J. D., and Martial, J. A. (1981).J. Biol. Chem. 256, 4007–4016.
Cunningham, B. C., Henner, D. J., and Wells, J. A. (1990).Science 247, 1461–1465.
Cunningham, B. C., and Wells, J. A. (1991).Proc. Natl. Acad. Sci. USA 88, 3407–3411.
D'Andrea, A. D., Fasman, G. D., and Lodish, H. F. (1989).Cell 58, 1023–1024.
DeNoto, F. M., Moore, D. D., and Goodman, H. M. (1981).Nuc. Acids. Res. 9, 3719–3730.
Devereux, J. R., Haeberli, P., and Smithies, O. (1984).Nucl. Acids Res. 12, 387–395.
Eisenberg, S. P., Brewer, M. T., Verderber, E., Heimdal, P., Brandhuber, B. J., and Thompson, R. C. (1991).Proc. Natl. Acad. Sci. USA 88, 5232–5236.
Finzel, B. C., Clancy, L. L., Holland, D. R., Muchmore, S. W., Watenpaugh, K. D., and Einspahr, H. M. (1989).J. Mol. Biol. 209, 779–791.
Finzel, B. C., Weber, P. C., Hardman, K. D., and Salemme, F. R. (1985).J. Mol. Biol. 186, 627–643.
Fung, M. C., Hapel, A. J., Ymer, S., Cohen, D. R., Johnson, R. M., Campbell, H. D., and Young, I. G. (1984).Nature 307, 233–237.
Garnier, J., Osguthorpe, D. J., and Robson, B. (1978).J. Mol. Biol. 120, 97–120.
Goodwin, R. G., Friend, D., Ziegler, S. F., Jerzy, R., Falk, B. A., Gimpel, S., Cosman, D., Dower, S. K., March, C. J., Namen, A. E., and Park, L. S. (1990).Cell 60, 941–951.
Goodwin, R. G., Lupton, S., Schmierer, A., Hjerrild, K. J., Jerzy, R., Clevenger, W., Gillis, S., Cosman, D., and Namen, A. E. (1989).Proc. Natl. Acad. Sci. USA 86, 302–306.
Gough, N. M., Gough, J., Metcalf, D., Kelso, A., Grail, D., Nicola, N. A., Burgess, A. W., and Dunn, A. R. (1984).Nature 309, 763–767.
Graves, B. J., Hatada, M. H., Hendrickson, W. A., Miller, J. K., Madison, V. S., and Satow, Y. (1990).Biochemistry 29, 2679–2684.
Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T., Kashiwamura, S.-I., Nakajima, K., Koyama, K., Iwamatsu, A., Tsunasawa, S., Sakiyama, F., Matsui, H., Takahara, Y., Tanaguchi, T., and Kishimoto, T. (1986).Nature 324, 73–76.
Jacobs, K., Shoemaker, C., Rudersdorf, R., Neill, S. D., Kaufmann, R. J., Mufson, A., Seehra, J., Jones, S. S., Hewick, R., Fritsch, E. F., Kawakita, M., Shimizu, T., and Miyake, T. (1985).Nature 313, 806–810.
Kashima, N., Nishi-Takaoka, C., Fujita, T., Taki, S., Yamada, G., Hamuro, J., and Taniguchi, T. (1985).Nature 313, 402–404.
Kaushansky, K., Brown, C. B., and O'Hara, P. J. (1990).Int. J. Cell Cloning 8 (Suppl. 1), 26–34.
Kinashi, T., Harada, N., Severinson, E., Tanabe, T., Sideras, P., Konishi, M., Azuma, C., Tominaga, A., Bergstedt-Lindqvist, S., Takahashi, M., Matsuda, F., Yaoita, Y., Takatsu, K., and Honjo, T. (1986).Nature 324, 70–73.
Kruttgen, A., Rose-John, S., Moller, C., Wroblowski, B., Wollmer, A., Mullberg, J., Hirano, T., Kishimoto, T., and Heinrich, P. (1990).FEBS Lett. 262, 323–326.
Lai, P.-H., Everett, R., Wang, F.-F., Arakawa, T., and Goldwasser, E. (1986).J. Biol. Chem. 261, 3116–3121.
Lederer, F., Glatigny, A., Bethge, P. H., Bellamy, H. D., and Mathews, F. S. (1981).J. Mol. Biol. 148, 427–448.
Lee, F., Yokota, T., Otsuka, T., Meyerson, P., Villaret, D., Coffman, R., Mosmann, T., Rennick, D., Roehm, N., Smith, C., Zlotnik, A., and Arai, K.-I. (1986).Proc. Natl. Acad. Sci. USA 83, 2061–2065.
Leutz, A., Damm, K., Sterneck, E., Kowenz, E., Ness, S., Frank, R., Gausepohl, H., Pan, Y.-C. E., Smart, J., Hayman, M., and Graf, T. (1989).EMBO J. 8, 175–181.
Lim, V. I. J. (1974).J. Mol. Biol. 88, 857–894.
Lin, F.-K., Suggs, S., Lin, C.-H., Browne, J. K., Smalling, R., Egrie, J. C., Chen, K. K., Fox, G. M., Martin, F., Stabinsky, Z., Badraw, S. M., Lai, P.-H., and Goldwasser, E. (1985).Proc. Natl. Acad. Sci. USA 82, 7580–7584.
Linzer, D. I. H., and Nathans, D. (1984).Proc. Natl. Acad. Sci. USA 81, 4255–4259.
Lokker, N. A., Zenke, G., Strittmatter, U., Fragg, B., and Movva, N. R. (1991).EMBO J. 10, 2125–2131.
Lu, H. S., Boone, T. C., Souza, L. M., and Lai, P.-H. (1989).Arch. Biochem. Biophys. 268, 81–92.
Lupton, S. D., Gimpel, S., Jerzy, R., Brunton, L. L., Hjerrild, K. A., Cosman, D., and Goodwin, R. G. (1990).J. Immunol. 144, 3592–3601.
Mathews, F. S., Argos, P., and Levine, M. (1972).Cold Spring Harbor Symp. Quant. Biol. 36, 387–395.
McDonald, J. D., Lin, F.-K., and Goldwasser, E. (1986).Mol. Cell. Biol. 6, 842–848.
Metcalf, D. (1989).Nature 339, 27–30.
Mizel, S. B. (1989).FASEB J. 3, 2379–2388.
Nagata, S., Tsuchiya, M., Asano, S., Kaziro, Y., Yamazaki, T., Yamamoto, O., Hirata, Y., Kubota, N., Oheda, M., Nomura, H., and Ono, M. (1986).Nature 319, 415–418.
Nicola, N. A. (1989).Ann. Rev. Biochem. 58, 45–77.
Nicola, N. A., and Metcalf, D. (1991).Cell 67, 1–4.
Ono, M., Takayama, Y., Rand-Weaver, M., Sakata, S., Yasunaga, T., Noso, T., and Kawauchi, H. (1990).Proc. Natl. Acad. Sci. USA 87, 4330–4334.
Page, G. S., Smith, S., and Goodman, H. M. (1981).Nuc. Acid. Res. 9, 2087–2104.
Parry, D. A. D., Minasian, E., and Leach, S. J. (1988).J. Mol. Recogn. 1, 107–110.
Paul, S. R., Bennett, F., Calvetti, J. A., Kelleher, K., Wood, C. R., O'Hara, Jr., R. M., Leary, A. C., Sibley, B., Clark, S. C., Williams, D. A., and Yang, Y.-C. (1990).Proc. Natl. Acad. Sci. USA 87, 7512–7516.
Paul, W. E. (1989).Cell 57, 521–524.
Presnell, S. R., and Cohen, F. E. (1989).Proc. Natl. Acad. Sci. USA 86, 6592–6596.
Shanafelt, A. B., Johnson, K. E., and Kastelein, R. A. (1991).J. Biol. Chem. 266, 13,804–13,810.
Shanafelt, A. B., and Kastelein, R. A. (1989).Proc. Natl. Acad. Sci. USA 86, 4872–4876.
Taniguchi, T., Matsui, H., Fujita, T., Takaoka, C., Kashima, N., Yoshimoto, R., and Hamuro, J. (1983).Nature 302, 305–310.
Tsuchiya, M., Asano, S., Kaziro, Y., and Nagata, S. (1986).Proc. Natl. Acad. Sci. USA 83, 7633–7637.
Van Snick, J., Cayphas, S., Szikora, J.-P., Renauld, J.-C., Van Roost, E., Boon, T., and Simpson, R. J. (1988).Eur. J. Immunol. 18, 193–197.
Ward, K. B., Hendrickson, W. A., and Klippenstein, G. L. (1975).Nature 257, 818–821.
Windsor, W. T., Syto, R., Le, H. V., and Trotta, P. P. (1991).Biochemistry 30, 1259–1264.
Wingfield, P., Graber, P., Moonen, P., Craig, S., and Pain, R. H. (1988).Eur. J. Biochem. 173, 65–72.
Wong, G. G., Witek, J. S., Temple, P. A., Wilkens, K. M., Leary, A. C., Luxenberg, D. P., Jones, S. S., Brown, E. L., Kay, R. M., Orr, E. C., Shoemaker, C., Golde, D. W., Kaufman, R. J., Hewick, R. M., Wang, E. A., and Clark, S. C. (1985).Science 228, 810–815.
Yang, Y.-C., Ciarletta, A. B., Temple, P. A., Chung, M. P., Kovacic, S., Witek-Giannotti, J. S., Leary, A. C., Kriz, R., Donahue, R. E., Wong, G. G., and Clark, S. C. (1986).Cell 47, 3–10.
Yang, Y.-C., Ricciardi, S., Ciarletta, A., Calvetti, J., Kelleher, K., and Clark, S. C. (1989).Blood 74, 1880–1884.
Yokota, T., Otsuka, T., Mosmann, T., Banchereau, J., DeFrance, T., Blanchard, D., DeVries, J. E., Lee, F., and Arai, K.-I. (1986).Proc. Natl. Acad. Sci. USA 83, 5894–5898.
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Manavalan, P., Swope, D.L. & Withy, R.M. Sequence and structural relationships in the cytokine family. J Protein Chem 11, 321–331 (1992). https://doi.org/10.1007/BF01024870
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DOI: https://doi.org/10.1007/BF01024870