Structural and functional analysis of rare missense mutations in human chorionic gonadotrophin β-subunit

Molecular Human Reproduction

Volumn 18, Issue 8, 2012, Pages 379-390

  Nagirnaja, Liina ^a   Venclovas, Česlovas ^b   Rull, Kristiina ^a   Jonas, Kim C ^c   Peltoketo, Hellevi ^c   Christiansen, Ole B ^d,e   Kairys, Visvaldas ^b   Kivi, Gaily ^f   Steffensen, Rudi ^e   Huhtaniemi, Ilpo T ^c   Laan, Maris ^a  

^a UNIVERSITY OF TARTU   (Estonia)

^b VILNIUS UNIVERSITY   (Lithuania)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

^d Rigshospitalet   (Denmark)

^e AALBORG UNIVERSITY HOSPITAL   (Denmark)

^f Icosagen Cell Factory OU   (Estonia)

Author keywords

CGB5 and CGB8; Female reproduction; Functional assays; HCG ; Missense mutations; Recurrent miscarriage; Structural analysis

Indexed keywords

ARGININE; CHORIONIC GONADOTROPIN ALPHA SUBUNIT; CHORIONIC GONADOTROPIN BETA SUBUNIT; GLYCOPEPTIDASE; LEUCINE; N ACETYL BETA GLUCOSAMINIDASE; RECOMBINANT ENZYME; VALINE;

ADULT; AMINO ACID SUBSTITUTION; ARTICLE; BIOASSAY; BIOLOGICAL ACTIVITY; CLINICAL ASSESSMENT; COMPUTER MODEL; CONFORMATION; CONTROLLED STUDY; DATA ANALYSIS; DENMARK; DIMERIZATION; ESTONIA; FEMALE; FINLAND; GENE MUTATION; HORMONE BLOOD LEVEL; HORMONE STRUCTURE; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; IN VITRO STUDY; MAJOR CLINICAL STUDY; MISSENSE MUTATION; MOLECULAR DYNAMICS; PATHOPHYSIOLOGY; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN FUNCTION; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; SIGNAL TRANSDUCTION; SPONTANEOUS ABORTION;

ABORTION, HABITUAL; AMINO ACID SEQUENCE; ANIMALS; BASE SEQUENCE; CELL LINE; CHO CELLS; CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN; CRICETINAE; FEMALE; HUMANS; MOLECULAR DYNAMICS SIMULATION; MUTATION, MISSENSE; PREGNANCY; PREGNANCY COMPLICATIONS; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, QUATERNARY; SEQUENCE ANALYSIS, DNA;

EID: 84864141655     PISSN: 13609947     EISSN: 14602407     Source Type: Journal    
DOI: 10.1093/molehr/gas018     Document Type: Article

References (55)

1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25:3389-3402.
2. Bedows E, Huth JR, Suganuma N, Bartels CF, Boime I, Ruddon RW. Disulfide bond mutations affect the folding of the human chorionic gonadotropin-beta subunit in transfected Chinese hamster ovary cells. J Biol Chem 1993;268:11655-11662.
3. Bedows E, Norton SE, Huth JR, Suganuma N, Boime I, Ruddon RW. Misfolded human chorionic gonadotropin beta subunits are secreted from transfected Chinese hamster ovary cells. J Biol Chem 1994; 269:10574-10580.
4. Ben-Menahem D, Hyde R, Pixley M, Berger P, Boime I. Synthesis of multi-subunit domain gonadotropin complexes: a model for alpha/ beta heterodimer formation. Biochemistry 1999;38:15070-15077.
5. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:64-67.
6. Bricker L, Farquharson RG. Types of pregnancy loss in recurrent miscarriage: implications for research and clinical practice. Hum Reprod 2002;17:1345-1350.
7. Christiansen OB, Mathiesen O, Lauritsen JG, Grunnet N. Idiopathic recurrent spontaneous abortion. Evidence of a familial predisposition. Acta Obstet Gynecol Scand 1990;69:597-601.
8. Crooks GE, Hon G, Chandonia JM, Brenner SE. WebLogo: a sequence logo generator. Genome Res 2004;14:1188-1190.
9. Darden T, York D, Pedersen L. Particle mesh Ewald: an N log(N) method for Ewald sums in large systems. J Chem Phys 1993;98: 10089-10092.
10. Fan QR, HendricksonWA. Structure of human follicle-stimulating hormone in complex with its receptor. Nature 2005;433:269-277.
11. Feng W, Matzuk MM, Mountjoy K, Bedows E, Ruddon RW, Boime I. The asparagine-linked oligosaccharides of the human chorionic gonadotropin beta subunit facilitate correct disulfide bond pairing. J Biol Chem 1995; 270:11851-11859.
12. Feng W, Bedows E, Norton SE, Ruddon RW. Novel covalent chaperone complexes associated with human chorionic gonadotropin beta subunit folding intermediates. J Biol Chem 1996;271:18543-18548.
13. Garcia-Campayo V, Boime I. Novel recombinant gonadotropins. Trends Endocrinol Metab 2001;12:72-77.
14. Guibourdenche J, Handschuh K, Tsatsaris V, Gerbaud P, Leguy MC, Muller F, Brion DE, Fournier T. Hyperglycosylated hCG is a marker of early human trophoblast invasion. J Clin Endocrinol Metab 2010; 95:E240-E244.
15. Hallast P, Nagirnaja L, Margus T, Laan M. Segmental duplications and gene conversion: human luteinizing hormone/chorionic gonadotropin beta gene cluster. Genome Res 2005;15:1535-1546.
16. Hallast P, Saarela J, Palotie A, Laan M. High divergence in primate-specific duplicated regions: human and chimpanzee chorionic gonadotropin beta genes. BMC Evol Biol 2008;8:195.
17. Hay DL. Placental histology and the production of human choriogonadotrophin and its subunits in pregnancy. Br J Obstet Gynaecol 1988;95:1268-1275.
18. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM. LINCS: a linear constraint solver for molecular simulations. J Comput Chem 1997; 18:1463-1472.
19. Hess B, Kutzner C, van der Spoel D, Lindahl E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 2008;4:435-447.
20. Huhtaniemi IT, Korenbrot CC, Jaffe RB. HCG binding and stimulation of testosterone biosynthesis in the human fetal testis. J Clin Endocrinol Metab 1977;44:963-967.
21. Jiang M, Savontaus ML, Simonsen H, Williamson C, Mullenbach R, Gromoll J, Terwort N, Alevizaki M, Huhtaniemi I. Absence of the genetic variant Val79Met in human chorionic gonadotropin-beta gene 5 in five European populations. Mol Hum Reprod 2004;10:763-766.
22. Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 1983;22:2577-2637.
23. Kajihara T, Uchino S, Suzuki M, Itakura A, Brosens JJ, Ishihara O. Human chorionic gonadotropin confers resistance to oxidative stress-induced apoptosis in decidualizing human endometrial stromal cells. Fertil Steril 2010;95:1302-1307.
24. Kayisli UA, Selam B, Guzeloglu-Kayisli O, Demir R, Arici A. Human chorionic gonadotropin contributes to maternal immunotolerance and endometrial apoptosis by regulating Fas-Fas ligand system. J Immunol 2003;171:2305-2313.
25. Kolte AM, Nielsen HS, Moltke I, Degn B, Pedersen B, Sunde L, Nielsen FC, Christiansen OB. A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage. Mol Hum Reprod 2011;17:379-385.
26. Korhonen J, Stenman UH, Ylostalo P. Serum human chorionic gonadotropin dynamics during spontaneous resolution of ectopic pregnancy. Fertil Steril 1994;61:632-636.
27. Kottler ML, Chou YY, Chabre O, Richard N, Polge C, Brailly-Tabard S, Chanson P, Guiochon-Mantel A, Huhtaniemi I, Young J. A new FSHbeta mutation in a 29-year-old woman with primary amenorrhea and isolated FSH deficiency: functional characterization and ovarian response to human recombinant FSH. Eur J Endocrinol 2010;162:633-641.
28. Lapthorn AJ, Harris DC, Littlejohn A, Lustbader JW, Canfield RE, Machin KJ, Morgan FJ, Isaacs NW. Crystal structure of human chorionic gonadotropin. Nature 1994;369:455-461.
29. Lopata A, Hay DL. The potential of early human embryos to form blastocysts, hatch from their zona and secrete HCG in culture. Hum Reprod 1989;4:87-94.
30. Maston GA, Ruvolo M. Chorionic gonadotropin has a recent origin within primates and an evolutionary history of selection. Mol Biol Evol 2002; 19:320-335.
31. Matzuk MM, Krieger M, Corless CL, Boime I. Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells. Proc Natl Acad Sci USA 1987;84:6354-6358.
32. Matzuk MM, Boime I. The role of the asparagine-linked oligosaccharides of the alpha subunit in the secretion and assembly of human chorionic gonadotrophin. J Cell Biol 1988;106:1049-1059.
33. Miller-Lindholm AK, LaBenz CJ, Ramey J, Bedows E, Ruddon RW. Human chorionic gonadotropin-beta gene expression in first trimester placenta. Endocrinology 1997;138:5459-5465.
34. Miller-Lindholm AK, Bedows E, Bartels CF, Ramey J, Maclin V, Ruddon RW. A naturally occurring genetic variant in the human chorionic gonadotropin-beta gene 5 is assembly inefficient. Endocrinology 1999;140:3496-3506.
35. Mishra AK, Mahale SD, Iyer KS. Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its beta-subunit: possible involvement of the disulfide bonds Cys(9)-Cys(57) and Cys(23)-Cys(72) in receptor binding of the hormone. J Pept Res 2001;58:17-26.
36. Mishra AK, Mahale SD, Iyer KS. Disulfide bonds Cys(9)-Cys(57), Cys(34)-Cys(88) and Cys(38)-Cys(90) of the b-subunit of human chorionic gonadotropin are crucial for heterodimer formation with the a-subunit: experimental evidence for the conclusions from the crystal structure of hCG. Biochim Biophys Acta 2003;1645:49-55.
37. Morgan FJ, Birken S, Canfield RE. The amino acid sequence of human chorionic gonadotropin. The alpha subunit and beta subunit. J Biol Chem 1975;250:5247-5258.
38. Murray-Rust J, McDonald NQ, Blundell TL, Hosang M, Oefner C, Winkler F, Bradshaw RA. Topological similarities in TGF-beta 2, PDGF-BB and NGF define a superfamily of polypeptide growth factors. Structure 1993;1:153-159.
39. Nagirnaja L, Rull K, Uuskula L, Hallast P, Grigorova M, Laan M. Genomics and genetics of gonadotropin beta-subunit genes: unique FSHB and duplicated LHB/CGB loci. Mol Cell Endocrinol 2010; 329:4-16.
40. Olechnovič K, Margelevicius M, Venclovas C. Voroprot: an interactive tool for the analysis and visualization of complex geometric features of protein structure. Bioinformatics 2011;27:723-724.
41. Pierce JG, Parsons TF. Glycoprotein hormones: structure and function. Annu Rev Biochem 1981;50:465-495.
42. Policastro PF, Daniels-McQueen S, Carle G, Boime I. A map of the hCG beta-LH beta gene cluster. J Biol Chem 1986;261:5907-5916.
43. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698-3703.
44. Rai R, Regan L. Recurrent miscarriage. Lancet 2006;368:601-611.
45. Rull K, Laan M. Expression of beta-subunit of HCG genes during normal and failed pregnancy. Hum Reprod 2005;20:3360-3368.
46. Rull K, Hallast P, Uuskula L, Jackson J, Punab M, Salumets A, Campbell RK, Laan M. Fine-scale quantification of HCG beta gene transcription in human trophoblastic and non-malignant non-trophoblastic tissues. Mol Hum Reprod 2008a;14:23-31.
47. Rull K, Nagirnaja L, Ulander VM, Kelgo P, Margus T, Kaare M, Aittomaki K, Laan M. Chorionic gonadotropin beta-gene variants are associated with recurrent miscarriage in two European populations. J Clin Endocrinol Metab 2008b;93:4697-4706.
48. Silla T, Hääl I, Geimanen J, Janikson K, Abroi A, Ustav E, Ustav M. Episomal maintenance of plasmids with hybrid origins in mouse cells. J Virol 2005; 79:15277-15288.
49. Sugahara T, Pixley MR, Minami S, Perlas E, Ben-Menahem D, Hsueh AJ, Boime I. Biosynthesis of a biologically active single peptide chain containing the human common alpha and chorionic gonadotropin beta subunits in tandem. Proc Natl Acad Sci USA 1995;92:2041-2045.
50. Tsampalas M, Gridelet V, Berndt S, Foidart JM, Geenen V, Perrier d'Hauterive S. Human chorionic gonadotropin: a hormone with immunological and angiogenic properties. J Reprod Immunol 2010; 85:93-98.
51. Uusküla L, Rull K, Nagirnaja L, Laan M. Methylation allelic polymorphism (MAP) in chorionic gonadotropin beta5 (CGB5) and its association with pregnancy success. J Clin Endocrinol Metab 2010;96:E199-E207.
52. van Gunsteren WF, Billeter SR, Eising AA, Hünenberger PH, Krüger P, Mark AE, Scott WRP, Tironi IG. Biomolecular Simulation: The GROMOS96 Manual and User Guide: Zürich, Germany: Vdf Hochschulverlag AG an der ETH Zürich, 1996.
53. Wu C, Narayan P, Puett D. Protein engineering of a novel constitutively active hormone-receptor complex. J Biol Chem 1996; 271:31638-42.
54. Zimmermann G, Ackermann W, Alexander H. Epithelial human chorionic gonadotropin is expressed and produced in human secretory endometrium during the normal menstrual cycle. Biol Reprod 2009; 80:1053-1065.
55. Zygmunt M, Herr F, Keller-Schoenwetter S, Kunzi-Rapp K, Munstedt K, Rao CV, Lang U, Preissner KT. Characterization of human chorionic gonadotropin as a novel angiogenic factor. J Clin Endocrinol Metab 2002;87:5290-5296.