The tie that binds: Design of biologically active single-chain human chorionic gonadotropins and a gonadotropin-receptor complex using protein engineering

Biology of Reproduction

Volumn 58, Issue 6, 1998, Pages 1337-1342

  Puett, David ^a   Wu, Chengbin ^a,b   Narayan, Prema ^a  

^a University of Georgia   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CHORIONIC GONADOTROPIN; COMPLEMENTARY DNA; CYCLIC AMP; DISULFIDE; FOLLITROPIN; GLYCOPROTEIN; GONADOTROPIN RECEPTOR; GROWTH FACTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; HORMONE RECEPTOR; HYDROFLUORIC ACID; LUTEINIZING HORMONE; LUTEINIZING HORMONE RECEPTOR; PROTEIN; SYNTHETIC PEPTIDE; THYROTROPIN;

AMINO ACID SEQUENCE; BINDING AFFINITY; GENETIC ENGINEERING; HUMAN; HUMAN CELL; IMMUNOBLOTTING; NONHUMAN; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN STRUCTURE; SHORT SURVEY; STRUCTURE ACTIVITY RELATION;

CHORIONIC GONADOTROPIN; DISULFIDES; HUMANS; MOLECULAR STRUCTURE; PROTEIN ENGINEERING; RECEPTORS, LH; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0031864755     PISSN: 00063363     EISSN: None     Source Type: Journal    
DOI: 10.1095/biolreprod58.6.1337     Document Type: Short Survey

References (71)

1. Lapthorn AJ, Harris DC, Little A, Lustbader JW, Canfield RE, Machin KJ, Morgan FJ, Isaacs NW. Crystal structure of human chorionic gonadotropin. Nature 1994; 369:455-461.
2. Wu H, Lustbader JW, Liu Y, Canfield RE, Hendrickson WA. Structure of human chorionic gonadotropin at 2.6A resolution from MAD analysis of the selenomethionyl protein. Structure 1994; 2:545-558.
3. Segaloff DL, Ascoli M. The lutropin/choriogonadotropin receptor . . . . 4 years later. Endocr Rev 1993; 14:324-347.
4. Koo YB, Ji I, Slaughter RG, Ji TH. Structure of the luteinizing hormone receptor gene and multiple exons of the coding sequence. Endocrinology 1991; 128:2297-2308.
5. Tsai-Morris CH, Buczko E, Wang W, Xie X-Z, Dufau ML. Structural organization of the rat luteinizing hormone (LH) receptor gene. J Biol Chem 1991; 266:11355-11359.
6. Ruddon RW, Sherman SA, Bedows E. Protein folding in the endoplasmic reticulum: lessons from the human chorionic gonadotropin β subunit. Protein Sci 1996; 5:1443-1452.
7. Gordon WL, Ward DN. Structural aspects of luteinizing hormone actions. In: Ascoli M (ed.), Luteinizing Hormone Action and Receptors. Boca Raton, FL: CRC Press, Inc.; 1985: 173-197.
8. Yadav SP, Brew K, Majercik MH, Puett D. A label selection approach to assess the role of individual amino groups in human choriogonadotropin-receptor binding. J Biol Chem 1994; 269:3991-3998.
9. Yadav SP, Brew K, Puett D. Holoprotein formation of human chorionic gonadotropin: differential trace labeling with acetic anhydride. Mol Endocrinol 1994; 8:1547-1558.
10. Salesse R, Bidart J-M, Troalen F, Bollet D, Garnier J. Peptide mapping of intersubunit and receptor interactions of human choriogonadotropin. Mol Cell Endocrinol 1990; 68:113-119.
11. Keutmann HT. Receptor-binding regions in human glycoprotein hormones. Mol Cell Endocrinol 1992; 86:C1-C6.
12. Dias JA. Progress and approaches in mapping the surfaces of human follicle-stimulating hormone. Comparison with the other human pituitary glycoprotein hormones. TEM 1992; 3:24-29.
13. Parsons TF, Pierce JG. Biologically active covalently cross-linked glycoprotein hormones and the effects of modification of the COOH-terminal region of their α-subunits. J Biol Chem 1979; 254:6010-6015.
14. Merz WE. Studies of the specific role of the subunits of choriogonadotropin for biological, immunological and physical properties of the hormone. Eur J Biochem 1979; 101:541-553.
15. Birken S, Gawinowicz Kolks MA, Amr S, Nisula B, Puett D. Tryptic digestion of the α subunit of human choriogonadotropin. J Biol Chem 1986; 261:10719-10727.
16. Birken S, Gawinowicz Kolks MA, Amr S, Nisula B, Puett D. Structural and functional studies of the tryptic core of the human chorionic gonadotropin β-subunit. Endocrinology 1987; 112:657-666.
17. Bousfield GR, Ward DN. Selective proteolysis of ovine lutropin or its β subunit by endoproteinase Arg-C. J Biol Chem 1988; 263:12602-12607.
18. Campbell RK, Dean-Emig DM, Moyle WR. Conversion of human choriogonadotropin into a follitropin by protein engineering. Proc Natl Acad Sci USA 1991; 88:760-764.
19. Matzuk MM, Boime I. Mutagenesis and gene transfer define site-specific roles of the gonadotropin oligosaccharides. Biol Reprod 1989; 40:48-53.
20. Suganuma N, Matzuk MM, Boime I. Elimination of disulfide bonds affects assembly and secretion of the human chorionic gonadotropin β subunit. J Biol Chem 1989; 264:19302-19307.
21. Azuma C, Miyai K, Saji F, Kamiura S, Tokugawa Y, Kimura T, Ohashi K, Koyama M, Iijima Y, Kashiwai T, Hayashizaki Y, Tanizawa O. Site-specific mutagenesis of human chorionic gonadotropin (hCG)-β subunit: influence of mutation on hCG production. J Mol Endocrinol 1990; 5:97-102.
22. Yoo J, Zeng H, Ji I, Murdoch WJ, Ji TH. COOH-terminal amino acids of the α subunit play common and different roles in human choriogonadotropin and follitropin. J Biol Chem 1993; 268:13034-13042.
23. 44 in the human gonadotropin α-subunit. J Biol Chem 1993; 268:21613-21617.
24. Puett D, Huang J, Xia H. Delineation of subunit and receptor contact sites by site-directed mutagenesis of hCGβ. In: Lustbader JW, Puett D, Ruddon RW (eds.), Glycoprotein Hormones: Structure, Function and Clinical Implications. New York: Serono Symposia, Springer-Verlag; 1994: 122-134.
25. Kikuchi T, Koyama M, Miyai K, Kimura T, Nishikiori N, Kimura T, Azuma C, Kusunoki M, Saji F, Tanizawa O. Loss of biological activity of human chorionic gonadotropin (hCG) by the amino acid substitution on the "CMGCC" region of the α-subunit. Mol Cell Endocrinol 1994; 102:1-7.
26. Furuhashi M, Ando H, Bielinska M, Pixley MR, Shikone T, Hseuh AJW, Boime I. Mutagenesis of cysteine residue in the human gonadotropin α subunit. J Biol Chem 1994; 269:25543-25548.
27. 90 of the α-subunit are crucial for receptor binding and hormone action of follicle-stimulation hormone (FSH) and play hormone-specific roles in FSH and human chorionic gonadotropin. Endocrinology 1995; 136:2948-2953.
28. Shao K, Purohit S, Bahl OP. Effect of modification of all loop regions in the α- and β-subunits of human choriogonadotropin on its signal transduction activity. Mol Cell Endocrinol 1996; 122:173-182.
29. Han Y, Bernard MP, Moyle WR. hCG-beta residues-94-96 alter LH activity without appearing to make key receptor contacts. Mol Cell Endocrinol 1996; 124:151-161.
30. Puett D, Bhowmick N, Fernandez LM, Huang J, Wu C, Narayan P. hCG-receptor binding and transmembrane signaling. Mol Cell Endocrinol 1996; 125:55-64.
31. Szkudlinski MW, The NG, Grossman M, Tropea JE, Weintraub BD. Engineering human glycoprotein hormone superactive analogues. Nat Biotechnol 1996; 14:1257-1263.
32. Grossman M, Szkudlinski MW, Dias JA, Xia H, Wong R, Puett D, Weintraub BD. Site-directed mutagenesis of arnino acids 33-44 of the common α-subunit reveals different structural requirements for heterodimer expression among the glycoprotein hormones and suggests that cyclic adenosine 3′,5′-monophosphate production and growth promotion are dissociable functions of human thyrotropin. Mol Endocrinol 1996; 10:769-779.
33. Dias JA, Zhang Y, Liu X. Receptor binding and functional properties of chimeric human follitropin prepared by an exchange between a small hydropholic intercystine loop of human follitropin and human lutropin. J Biol Chem 1994; 269:25289-25294.
34. Xie YB, Wang H, Segaloff DL. Extracellular domain of lutropin/choriogonadotropin receptor expressed in transfected cells binds choriogonadotropin with high affinity. J Biol Chem 1990; 265:21411-21414.
35. Tsai-Morris CH, Buczko E, Wang W, Dufau ML. Intronic nature of the rat luteinizing hormone receptor gene defines a soluble receptor subspecies with hormone binding activity. J Biol Chem 1990; 265: 19385-19388.
36. Ji I, Ji TH. Exons 1-10 of the rat LH receptor encode a high affinity hormone binding site and exon 11 encodes G-protein modulation and a potential second hormone binding site. Endocrinology 1991; 128: 2648-2650.
37. Moyle WR, Bernard MP, Myers RV, Marko OM, Strader CD. Lutropin/beta-adrenergic receptor chimeras bind choriogonadotropin and adrenergic ligands but are not expressed at the cell surface. J Biol Chem 1991; 266:10807-10812.
38. 383 in the second transmembrane domain of the lutropin receptor is important for high affinity hormone binding and cAMP production. J Biol Chem 1991; 266:14953-14957.
39. 397 is important for receptor activation. J Biol Chem 1993; 268:20851-20854.
40. Quintana J, Wang H, Ascoli M. The regulation of the binding affinity of the luteinizing hormone/choriogonadotropin receptor by sodium ions is mediated by a highly conserved aspartate located in the second transmembrane domain of G protein-coupled receptors. Mol Endocrinol 1993; 7:767-775.
41. Huang J, Puett D. Identification of two amino acid residues on the extracellular domain of the lutropin/choriogonadotropin receptor important in signaling. J Biol Chem 1995; 270:30023-30028.
42. 583 in the third extracellular loop of the lutropin/chorio-gonadotropin receptor is critical for signaling. J Biol Chem 1996; 271:925-930.
43. Ryu K-S, Gilchrist RL, Ji I, Kim S-J, Ji TH. Exoloop 3 of the luteinizing hormone/chorio-gonadotropin receptor. J Biol Chem 1996; 271: 7301-7304.
44. Fernandez LM, Puett D. Identification of amino acid residues in transmembrane helices VI and VII of the lutropin/choriogonadotropin receptor important in signaling. Biochemistry 1996; 35:3986-3993.
45. Thomas D, Rozell TG, Liu X, Segaloff DL. Mutational analyses of the extracellular domain of the full-length lutropin/choriogonadotropin receptor suggest leucine-rich repeats 1-6 are involved in hormone binding. Mol Endocrinol 1996; 10:760-768.
46. Moyle WR, Campbell RK, Rao SNV, Ayad NG, Bernard MP, Han Y, Wang Y. Model of human chorionic gonadotropin and lutropin receptor interaction that explains signal transduction of the glycoprotein hormones. J Biol Chem 1995; 270:20020-20032.
47. Henderson R, Baldwin JM, Ceska TA, Zemlin F, Beckmann E, Downing KH. Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. J Mol Biol 1990; 213:899-926.
48. Pebay-Peyroula E, Rummel G, Rosenbusch JP, Landau EM. X-ray structure of bacteriorhodopsin at 2.5 Angstroms from microcrystals grown in lipidic cubic phases. Science 1997; 277:1676-1681.
49. Kimura Y, Vassylyev DG, Miyazawa A, Kidera A, Matsushima M, Mitsuoka K, Murata K, Hirai T, Fujiyoshi Y. Surface of bacteriorhodopsin revealed by high-resolution electron crystallography. Nature 1997; 389:206-211.
50. Schertler GF, Villa C, Henderson R. Projection structure of rhodopsin. Nature 1993; 362:770-772.
51. McFarland KC, Sprengel R, Phillips HS, Kohler M, Rosemblit N, Nikolis K, Segaloff DL, Seeburg PH. Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. Science 1989; 245:494-499.
52. Braun T, Schofield PR, Sprengel R. Amino-terminal leucine-rich repeats determine hormone selectivity. EMBO J 1991; 10:1885-1890.
53. Kobe B, Deisenhofer J. Crystal structure of porcine ribonuclease inhibitor a protein with leucine-rich repeats. Nature 1993; 366:751-756.
54. Jiang X, Dreano M, Buckler DR, Cheng S, Ythier A, Wu H, Hendrickson WA, El Tayar N. Structural predictions for the ligand binding region of glycoprotein hormone receptors and the nature of hormone receptor interactions. Structure 1995; 3:1341-1353.
55. Kajava V, Vassart G, Wodak S. Modeling of the three dimensional structure of proteins with the typical leucine-rich repeats. Structure 1995; 3:867-877.
56. Couture L, Naharisa H, Grebert D, Remy J-J, Pajot-Augy E, Bozon V, Haertle J, Salesse R. Peptide and immunochemical mapping of the ectodomain of the porcine LH receptor. J Mol Endocrinol 1996; 16: 15-25.
57. Bhowmick N, Huang J, Puett D, Issacs NW, Lapthorn AJ. Determination of residues important in hormone binding to the extracellular domain of the luteinizing hormone/chorionic gonadotropin receptor by site-directed mutagenesis and modeling. Mol Endocrinol 1996; 10: 1147-1159.
58. Baldwin JM. The probable arrangement of the helices in G protein-coupled receptors. EMBO J 1993; 12:1693-1703.
59. Themmen APN, Martens JWM, Brunner HG. Gonadotropin receptor mutations. J Endocrinol 1997; 153:179-183.
60. Narayan P, Wu C, Puett D. Functional expression of yoked human chorionic gonadotropin in baculovirus-infected insect cells. Mol Endocrinol 1995; 9:1720-1726.
61. Sugahara T, Pixley MR, Minami S, Perlas E, Ben-Menahem D, Hsueh AJW, Boime I. Biosynthesis of α biologically active single chain containing the human common α and chorionic gonadotropin β subunits in tandem. Proc Natl Acad Sci USA 1995; 92:2041-2045.
62. Sugahara T, Grootenhuis PDJ, Sato A, Kudo M, Ben-Menahem D, Pixley MR, Hsueh AJW, Boime I. Expression of biologically active fusion genes encoding the common α subunit and either the CGβ or FSHβ subunits: role of a linker sequence. Mol Cell Endocrinol 1996; 125:71-77.
63. Heikoop JC, Van Beuningen-De Vaan MMJACM, Van Den Boogaart P, Grootenhuis PDJ. Evaluation of subunit truncation and the nature of the spacer for single chain human gonadotropins. Eur J Biochem 1997; 245:656-662.
64. Heikoop JC, Van Den Boogaart P, Mulders JWM, Grootenhuis PDJ. Structure-based design and protein engineering of intersubunit disulfide bonds in gonadotropins. Nat Biotechnol 1997; 15:658-662.
65. Wu C, Narayan P, Puett D. Protein engineering of a novel constitutively active hormone-receptor complex. J Biol Chem 1996; 271: 31638-31642.
66. Garcia-Campayo V, Sato A, Hirsch B, Sugahara T, Muyan M, Hsueh AJW, Boime I. Design of stable biologically-active recombinant lutropin analogs. Nat Biotechnol 1997; 15:663-667.
67. Ben-Menahem D, Kudo M, Pixley MR, Sato A, Suganuma N, Perlas E, Hsueh AJW, Boime I. The biologic action of single-chain choriogonadotropin is not dependent on the individual disulfide bonds of the β subunit. J Biol Chem 1997; 272:6827-6830.
68. Sato A, Perlas E, Ben-Menahem D, Kudo M, Pixley MR, Furuhashi M, Hsueh AJW, Boime I. Cystine knot of the gonadotropin α subunit is critical for intracellular behavior but not for in vitro biological activity. J Biol Chem 1997; 272:18098-18103.
69. Wu C, Narayan P, Puett D. hCGβ is capable of activating a yoked α subunit-LH/CG receptor. In: Program of the 79th annual meeting of the Endocrine Society; 1997; Minneapolis, MN. Abstract P2-395.
70. Ben-Menahem D, Boime I. Converting heterodimeric gonadotropins to genetically linked single chains. TEM 1996; 7:100-105.
71. Grossman M, Wong R, Szkudlinski MW, Weintraub BD. Human thyroid-stimulating hormone (hTSH) subunit gene fusion produces hTSH with increased stability and serum half-life and compensates for mutagenesis-induced defects in subunit association. J Biol Chem 1997; 272:21312-21316.