Human follitropin heterodimerization and receptor binding structural motifs: Identification and analysis by a combination of synthetic peptide and mutagenesis approaches

Molecular and Cellular Endocrinology

Volumn 125, Issue 1-2, 1996, Pages 45-54

  Dias, James A ^a,b  

^a WADSWORTH CENTER   (United States)

^b STATE UNIVERSITY OF NEW YORK   (United States)

Author keywords

Heterodimerization; Human follitropin; Receptor binding

Indexed keywords

ANTIBODY; CHORIONIC GONADOTROPIN; FOLLITROPIN; FOLLITROPIN RECEPTOR; GLYCOPROTEIN; PROTEIN SUBUNIT; SYNTHETIC PEPTIDE;

CONFERENCE PAPER; DIMERIZATION; HORMONE RECEPTOR INTERACTION; HORMONE STRUCTURE; MUTAGENESIS; PRIORITY JOURNAL; RADIORECEPTOR ASSAY; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; DIMERIZATION; FOLLICLE STIMULATING HORMONE; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MUTAGENESIS; PROTEIN STRUCTURE, SECONDARY; RECEPTORS, FSH;

EID: 0030596139     PISSN: 03037207     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0303-7207(96)03947-0     Document Type: Conference Paper

References (73)

1. [1] Ryan, R.J., Charlesworth, M.C., McCormick, D.J., Milius, R.P. and Keutmann, H.T. (1988) The glycoprotein hormones: recent studies of structure-function relationships. FASEB J. 2, 2661-2669.
2. [2] Ryan, R.J., Keutmann, H.T., Charlesworth, M.C., McCormick, D.J., Milius, R.P., Calvo, F.O. and Vutyavanich, T. (1987) Structure-function relationships of gonadotropins. Recent. Prog. Horm. Res. 43, 383-429.
3. [3] Ward, D.N. (1978) Chemical approaches to the structure-function relationships of luteinizing hormone (Lutropin). In: Structure and Functions of the Gonadotropins (McKerns, K.W., ed.), pp. 31-45, Plenum Press, New York.
4. [4] Morbeck, D.E., Charlesworth, M.C., Reed, D.K. and McCormick, D.J. (1993) Analysis of hormone-receptor interaction sites using synthetic peptides: receptor binding regions of the α-subunit of human choriogonadotropin. Methods 5, 191-200.
5. [5] Keutmann, H.T. (1992) Receptor-binding regions in human glycoprotein hormones. Mol. Cell. Endocrinol. 86, C1-C6.
6. [6] Leng, N., Grasso, P., Deziel, M.R. and Reichert, L.E. (1995) A synthetic peptide corresponding to glycoprotein hormone α-subunit residues 32-46 inhibits gonadotropin binding to receptor. Peptide Res. 8, 272-277.
7. [7] Dias, J.A. (1992) Progress and approaches in mapping the surfaces of human follicle stimulating hormone: Comparison with the other human pituitary glycoprotein hormones. Trends Endocrinol. Metab. 3, 24-29.
8. [8] Lapthorn, A.P., Harris, D.C., Littlejohn, A., Lustbader, J.W., Canfield, R.E., Machlin, K.J., Morgan, F.J. and Isaacs, N.W. (1994) Crystal structure of human chorionic gonadotropin. Nature 369, 455-461.
9. [9] Wu, H., Lustbader, J.W., Liu, Y., Canfield, R.E. and Hendrickson, W.A. (1994) Structure of human chorionic gonadotropin at 2.6 Å resolution from MAD analysis of the selenomethionyl protein. Structure 15, 545-558.
10. [10] Cunningham, B.C. and Wells, J.A. (1993) Comparison of a structural and functional epitope. J. Mol. Biol. 234, 554-563.
11. [11] Li, B., Tom J.Y.K., Oare, D., Yen, R., Fairbrother, W.J., Wells, J.A. and Cunningham, B.C. (1995) Minimization of a polypeptide hormone. Science 270, 1657-1660.
12. [12] Krystek, S.R., Dias, J.A. and Andersen, T.T. (1992) Identification of a subunit contact site of the α-subunit of follitropin. Peptide Res. 5, 165-168.
13. [13] Krystek, S.R., Dias, J.A. and Andersen, T.T. (1991) Identification of subunit contact sites on the α-subunit of lutropin. Biochemistry 30, 1858-1864.
14. [14] Vakharia, D.D., Dias, J.A. and Andersen, T.T. (1991) Determination of subunit contact associated epitopes of the β-subunit of human follicle stimulating hormone. Endocrinology 128, 1797-1804.
15. [15] Weiner, R.S. and Dias, J.A. (1992) Identification of assembled epitopes on the α-subunit of human follicle stimulating hormone. Mol. Cell. Endocrinol. 85, 41-52.
16. [16] Weiner, R.S., Dias, J.A. and Andersen, T.T. (1991) Epitope mapping of a monoclonal antibody to human FSHα identifies a potential receptor binding sequence. Endocrinology 128, 1485-1495.
17. [17] Vakharia, D.D., Dias, J.A., Andersen, T.T., Thakur, A.N. and O'Shea, A. (1990) Mapping of an assembled epitope of human FSHβ utilizing monoclonal antibodies, synthetic peptides and hormone-receptor inhibition. Endocrinology 127, 658-666.
18. [18] Vakharia, D.D., Bryant, S.H. and Dias, J.A. (1992) Topographic analysis of human follicle-stimulating hormone-β using anti-peptide antisera. Mol. Cell. Endocrinol. 85, 89-97.
19. [19] Weiner, R.S., Andersen, T.T. and Dias, J.A. (1990) Topographic analysis of the α-subunit of human follicle-stimulating hormone using site-specific antipeptide antisera. Endocrinology 127, 573-579.
20. [20] Labbe-Jullie, C., Sergi, I., Canonne, C., Darbon, H. and Ronin, C. (1992) Comparative mapping of human Thyrotropin, Gonadotropin and free subunits with antipeptide antibodies. Endocrinology 131, 1999.
21. [21] Chaturvedi, S. and Bahl, O.P. (1990) Synthesis of cystine peptides 21-25/70-73 and 35-39/56-59 of the β-subunit of human chorionic gonadotropin. Int. J. Pep. Protein Res. 35, 133-140.
22. [22] Troalen, F., Razafindratsita, A., Puisieux, A., Voeltzel, T., Bohoun, C., Bellet, D. and Bidart, J. (1990) Structural probing of human lutropin using antibodies raised against synthetic peptides constructed by classical and multiple antigen peptide system approaches. Mol. Immunol. 27(4), 363-368.
23. [23] Keutmann, H.T., Charlesworth, M.C., Kitzmann, K., Mason, K.A., Johnson, L. and Ryan, R.J. (1988) Primary and secondary structural determinants in the receptor binding sequence β-(38-57) from human luteinizing hormone. Biochemistry 27, 8939-8944.
24. [24] Reichert, L.E. (1994) The functional relationship between FSH and its receptor as studied by synthetic peptide strategies. Mol. Cell. Endocrinol. 100, 21-27.
25. [25] Campbell, R.K., Dean-Emig, D.M. and Moyle, W.R. (1991) Conversion of human choriogonadotropin into a follitropin by protein engineering. Proc. Natl. Acad. Sci. 88, 760-764.
26. [26] Keutmann, H.T., Schneyer, A.L., Kitzmann, K.A. and Roche, P.C. (1995) A universal β-subunit binding loop determinant shared by human LH and FSH. Proc. Endocrinol. Soc. 77th Annual Meeting, p. 141 (Abstract).
27. [27] Keutmann, H.T., Hua, Q. and Weiss, M.A. (1992) Structure of a receptorbinding fragment from human luteinizing hormone β-subunit determined by [1H]- and [15N]-Nuclear magnetic, resonance spectroscopy. Mol. Endocrinol. 6, 904-913.
28. [28] Yarney, T.A., Sairam, M.R., Khan, H., Ravindranath, N., Payne, S. and Seidah, N.G. (1993) Molecular cloning and expression of the ovine testicular follicle stimulating hormone receptor. Mol. Cell. Endocrinol. 93, 219-226.
29. [29] Roth, K.E. and Dias, J.A. (1995) Scanning alanine mutagenesis of long loop residues 33-53 in follicle stimulating hormone β-subunit. Mol. Cell. Endocrinol. 109, 143-149.
30. [30] Chen, F. and Puett, D. (1991) Contributions of Arginies-43 and -94 of human choriogonadotropin β to receptor binding and activation as determined by oligonucleotide-based mutagenesis. Biochemistry 30, 10171-10175.
31. [31] Bousfield, G.R. and Ward, D.N. (1988) Selective proteolysis of ovine lutropin or its β-subunit by endoproteinase Arg-C. J. Biol. Chem. 263(25), 12602-12607.
32. [32] Birken, S., Kolks, M.A.G., Amr, S., Nisula, B. and Puett, D. (1987) Structural and functional studies of the tryptic core of the human chorionic gonadotropin subunit. Endocrinology 112, 657-666
33. [33] Valove, F.M., Finch, C., Anasti, J.N., Froelich, J. and Flack, M.R. (1994) Receptor binding and signal transduction are dissociable functions requiring different sites on follicle-stimulating hormone. Endocrinology 135, 2657-2661.
34. [34] Santa Coloma, T.A., Dattatreyamurty, B. and Reichert, L.E. (1990) A synthetic peptide corresponding to human FSH β-subunit 33-53 binds to FSH receptor, stimulates basal estradiol biosynthesis and is a partial antagonist of FSH. Biochemistry 29, 1194-1200.
35. [35] Santa-Coloma, T.A., Crabb, J.W. and Reichert, L.E. (1991) A synthetic peptide encompassing two discontinuous regions of hFSHyβ-subunit mimics the receptor binding surface of the hormone. Mol. Cell. Endocrinol. 78, 197-204.
36. [36] Roth, R.E. and Dias, J.A. (1996) Follitropin conformational stability mediated by loop 2B effects follitropin-receptor interaction. Biochemistry 35, 7928-7935.
37. [37] Bidart, J.M., Troalen, F., Bohuon, C. and Bellet, D.H. (1989) Analysis of topolographic antigenic determinants on human choriogonadotropin using synthetic peptides. UCLA Symposia on Molecular and Cellular Biology 86, 223-237.
38. [38] Liu, C. and Dias, J.A. (1996) Long loop residues 33-58 in the human glycoprotein hormone common α-subunit contain structural components for subunit heterodimerization and human follitropin receptor binding. Arch. Biochem. Biophys. 329, 127-135.
39. [39] Salesse, R., Bidart, J.M., Troalen, F., Bellet, D. and Garnier, J. (1990) Peptide mapping of intersubunit and receptor interactions of human choriogonadotropin. Mol. Cell. Endocrinol. 68, 113-119.
40. [40] Santa Coloma, T.A. and Reichert, L.E. Jr. (1991) Determination of α-subunit contact regions of human follicle-stimulating hormone β-subunit using synthetic peptides. J. Biol. Chem. 266, 2759-2762.
41. [41] Roth, K.E., Liu, C., Shepard, B.A., Shaffer, J.B. and Dias, J.A. (1993) The flanking amino acids of the human follitropin β-subunit 33-53 region are involved in assembly of the follitropin heterodimer. Endocrinology 132, 2571-2577.
42. [42] Xia, H. and Puett, D. (1994) Identification of conserved amino acid residues in the β-subunit of human choriogonadotropin important in holoprotein formation. J. Biol. Chem. 269, 17944-17953.
43. [43] Weiss, J., Axelrod, L., Whitcomb, R.W., Harris, P.E., Crowley, W.F. and Jameson, J.L. (1992) Hypogonadism caused by a single amino acid substitution in the β-subunit of luteinizing hormone. New Engl. J. Med. 326, 179-183.
44. [44] Huang, J. and Puett, D. (1995) On the role of the invariant glutamine at position 54 in the human choriogonadotropin β-subunit. Mol. Cell. Biochem. 136, 183-186.
45. [45] Ward, D.N. and Moore, W.T. (1979) Comparative study of mammalian glycoprotein hormones. In: Animal Mode is for Research on Contraception and Fertility (Alexander, N.J., ed.), pp. 151-164, Harper and Row, Baltimore.
46. [46] Coloma, T.A. and Reichert, L.E. Jr. (1990) Identification of a follicle-stimulating hormone receptor-binding region in hFSH-β-(81-95) using synthetic peptides. J. Biol. Chem. 265, 5037-5042.
47. [47] Grasso, P., Santa-Coloma, T.A., Boniface, J.J. and Reichert, L.E., Jr. (1991) A synthetic peptide corresponding to hFSH-β-(81-95) has thioredoxin-like activity. Mol. Cell. Endocrinol. 78, 163-170.
48. [48] Morbeck, D.E., Roche, P.C., Keutmann, H.T. and McCormick, D.J. (1993) A receptor binding site identified in the region 81-95 of the β-subunit of human luteinizing hormone (LH) and chorionic gonadotropin (hCG). Mol. Cell. Endocrinol. 97, 173-181.
49. [49] Keutmann, H.T., Mason, K.A., Kitzmann, K. and Ryan, R.J. (1989) Role of the β93-100 determinant loop sequence in receptor binding and biological activity of human luteinizing hormone and chorionic gonadotropin. Mol. Endocrinol. 3, 526-531.
50. [50] Morris, J.C., McCormick, D.J. and Ryan, R.J. (1990) Inhibition of thyrotropin binding to receptor by synthetic human thyrotropin β peptides. J. Biol. Chem. 265, 1881-1884.
51. [51] Leinung, M.C., Bergen, E.R., McCormick, D.J. and Morris, J.C. (1992) Synthetic analogs of the carboxyl-terminus of β-thyrotropin: The importance of basic amino acids in receptor binding activity. Biochemistry 31, 10094-10098.
52. [52] Bidart, J.M., Troalen, F., Ghillani, P., Rouas, N., Razafindratsita, A., Bohuon, C. and Bellet, D. (1990) Peptide immunogen mimicry of a protein-specific structural epitope on human choriogonadotropin, Science 248, 736-739.
53. [53] Moyle, W.R., Campbell, R.K., Myers, R.V., Bernard, M.P., Han, Y. and Wang, X. (1994) Co-evolution of ligand receptor pairs. Nature 368, 251-255.
54. [54] Dias, J.A., Zhang, Y. and Liu, X. (1994) Receptor binding and functional properties of chimeric human follitropin prepared by an exchange between a small hydrophilic inter-cysteine loop of human follitropin and human lutropin. J. Biol. Chem. 269, 25289-25294.
55. [55] Chen, F., Wang, Y. and Puett, D. (1991) Role of the invariant aspartic acid 99 of human choriogonadotropin Pin receptor binding activity. J. Biol. Chem. 266, 19357-19361.
56. [56] Chen, F. and Puett, D. (1992) A single amino acid residue replacement in the β-subunit of human chorionic gonadotrophin results in the loss of biological activity. J. Mol. Endocrinol. 8, 87-89.
57. [57] Lindau-Shepard, B., Roth, K.E. and Dias, J.A. (1994) Identification of amino acids in the C-terminal region of human follicle-stimulating hormone (FSH) β-subunit involved in binding to human FSH receptor. Endocrinology 135, 1235-1240.
58. [58] Huang, J., Ujihara, M., Xia, H., Chen, F., Yoshida, H. and Puett, D. (1993) Mutagenesis of the determinant loop region of the human choriogonadotropin β. Mol. Cell. Endocrinol. 90, 211-218.
59. [59] DeBeer, T., Van Zuylen, C.W.E.M., Leeflang, B.R., Hard, K., Boelens, R., Kaptein, R., Kamerling, J.P. and Vliegenthart, J.F.G. (1996) NMR studies of the free alpha subunit of human chronic gonadotropin 241, 229-242.
60. [61] Leinung, M.C., Reed, D.K., McCormick, D.J., Ryan, R.J. and Morris, J.C. (1991) Further characterization of the receptor-binding region of the thyroid stimulating hormone α-subunit: A comprehensive synthetic peptide study of the α-subunit 26-46 sequence. Proc. Natl. Acad. Sci. 88, 9707-9711.
61. [62] Reed, D.K., Ryan, R.J. and McCormick, D.J. (1991) Residues in the a subunit of human choriotropin that are important for interaction with the lutropin receptor. J. Biol. Chem. 266, 14251-14255.
62. [63] Erickson, L.D., Rizza, S.A., Bergert, E.R., Charlesworth, M.C., McCormick, D.J. and Ryan, R.J. (1990) Synthetic α-subunit peptides stimulate testosterone production in vitro by rat Leydig cells. Endocrinology 126, 2555-2560.
63. [64] Liu, C., Roth, K.E., Lindau-Shepard, B.A., Shaffer, J.B. and Dias, J.A. (1993) Site directed alanine mutagenesis of F33, R35 and 42RSK44 in the human gonadotropin α-subunit. J. Biol. Chem. 268, 21613-21617.
64. [65] Xia, H., Chen, F. and Puett, D. (1994) A region in the human glycoprotein hormone α-subunit important in holoprotein formation and receptor binding. Endocrinology 134, 1768-1770.
65. [66] Flack, M.R., Froehlich, J., Bennet, A.P., Anasti, J. and Nisula, B.C. (1994) Site-directed mutagenesis defines the individual roles of the glycosylation sites on follicle-stimulating hormone. J. Biol. Chem. 269, 14015-14020.
66. [67] Bidart, J.M., Troalen, F., Bousfield, G.R., Birken, S. and Bellet, D.H. (1988) Antigenic determinants on human choriogonadotropin α-subunit. I. Characterization of topographic sites recognized by monoclonal antibodies. J. Biol. Chem. 263, 10364-10369.
67. [68] Nishimura, R., Shin, J., Ji, I., Middaugh, C.R., Kruggel, W., Lewis, R.V. and Ji, T.H. (1986) A single amino acid substitution in an ectopic a subunit of a human carcinoma choriogonadotropin. J. Biol. Chem. 261, 10475-10477.
68. [69] Troalen, F., Bellet, D.H., Ghillani, P., Puisieux, A., Bohuon, C.J. and Bidart, J.M. (1988) Antigenic determinants on human choriogonadotropin α-subunit II. Immunochemical mapping by a monodonal antipeptide antibody. J. Biol. Chem. 263, 10370-10376.
69. [70] Chen, F., Wang, Y. and Puett, D. (1992) The carboxy-terminal region of the glycoprotein hormone α-subunit: contributions to receptor binding and signaling in human chorionic gonadotropin. Mol. Endocrinol. 6, 914-919.
70. [71] Yoo, J., Zeng, H., Ji, I., Murdoch, W.J. and Ji, T.H. (1993) COOH-terminal amino acids of the α-subunit play common and different roles in human choriogonadotropin and follitropin. J. Biol. Chem. 268, 13034-13042.
71. [72] Zeng, H., Ji, I. and Ji, T.H. (1995) Lys-91 and His-90 of the α-subunit are crucial for receptor binding and hormone action of follicle stimulating hormone and play hormone-specific roles in FSH and human chorionic gonadotropin. Endocrinology 138, 2498-2953.
72. [73] Yoo, J., Ji, I. and Ji, T.H. (1991) Conversion of lysine 91 to methionine or glutamic acid in human choriogonadotropin a results in the loss of cAMP inducibility. J. Biol. Chem. 266, 17741-17743.
73. [74] Grossman, M., Szkudlinski, M.W., Zeng, H., Kraiem, Z., Ji, I., Tropea, J.E., Ji, T.H. and Weintraub, B.D. (1995) Role of the carboxy-terminal residues of the α-subunit in the expression and bioactivity of human thyroid-stimulating hormone. Mol. Endocrinol. 9, 948-958.