Insight into mutation-induced activation of the luteinizing hormone receptor: Molecular simulations predict the functional behavior of engineered mutants at M398

Molecular Endocrinology

Volumn 18, Issue 6, 2004, Pages 1499-1508

  Fanelli, Francesca ^a   Verhoef Post, Miriam ^b   Timmerman, Marianna ^b   Zeilemaker, Annelieke ^b   Martens, John W M ^b   Themmen, Axel P N ^b  

^a UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

^b ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

LUTEINIZING HORMONE RECEPTOR;

AB INITIO CALCULATION; AMINO ACID SUBSTITUTION; ARTICLE; COMPUTER MODEL; COMPUTER PREDICTION; COMPUTER SIMULATION; CONTROLLED STUDY; GENETIC SCREENING; HORMONE DETERMINATION; HUMAN; HUMAN CELL; INDUCED MUTATION; MOLECULAR SIZE; PRIORITY JOURNAL; PROTEIN ENGINEERING; PROTEIN LOCALIZATION; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; RECEPTOR INTRINSIC ACTIVITY; REDUCTION; SITE DIRECTED MUTAGENESIS; STRUCTURE ANALYSIS;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; BINDING SITES; CELL LINE; CYCLIC AMP; CYTOSOL; DNA, COMPLEMENTARY; DOSE-RESPONSE RELATIONSHIP, DRUG; GENES, REPORTER; HUMANS; KINETICS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTAGENESIS; MUTAGENESIS, SITE-DIRECTED; MUTATION; OLIGONUCLEOTIDES; PLASMIDS; PROTEIN BINDING; PROTEIN CONFORMATION; RECEPTORS, LH; RHODOPSIN; SEQUENCE HOMOLOGY, AMINO ACID; SOFTWARE; TIME FACTORS; TRANSFECTION; TYROSINE;

EID: 2542498612     PISSN: 08888809     EISSN: None     Source Type: Journal    
DOI: 10.1210/me.2003-0050     Document Type: Article

References (34)

1. Ascoli M, Fanelli F, Segaloff DL 2002 The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev 23:141-174
2. Fanelli F, Puett D 2002 Structural aspects of the luteinizing hormone receptor: information from molecular modeling and mutagenesis. Endocrine 18:285-293
3. Fanelli F, Themmen APN, Puett D 2001 Lutropin receptor function: insights from natural, engineered and computer-simulated mutations. IUBMB Life 51:149-155
4. Themmen APN, Huhtaniemi I 2000 Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 21:551-583
5. Themmen APN, Martens JWM, Brunner HG 1998 Activating and inactivating mutations in LH receptors. Mol Cell Endocrinol 145:137-142
6. Latronico AC, Shinozaki H, Guerra Jr G, Pereira MA, Lemos Marini SH, Baptista MT, Arnhold IJ, Fanelli F, Mendonca BB, Segaloff DL 2000 Gonadotropin-independent precocious puberty due to luteinizing hormone receptor mutations in Brazilian boys: a novel constitutively activating mutation in the first transmembrane helix. J Clin Endocrinol Metab 85:4799-4805
7. Lin Z, Shenker A, Pearlstein R 1997 A model of the lutropin/ choriogonadotropin receptor: insights into the structural and functional effects of constitutively activating mutations. Protein Eng 10:501-510
8. Fanelli F 2000 Theoretical study on mutation-induced activation of the luteinizing hormone receptor. J Mol Biol 296:1333-1351
9. Angelova K, Fanelli F, Puett D 2002 Engineered and simulated mutations in transmembrane helices 6 and 7 of the lutropin receptor: a model for constitutive and ligand-mediated receptor activation. J Biol Chem 277:32202-32213
10. Ballesteros JA, Weinstein H 1995 Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods Neurosci 25:366-428
11. Kraaij R, Post M, Kremer H, Milgrom E, Epping, W, Brunner HG, Grootegoed JA, Themmen APN 1995 A missense mutation in the second transmembrane segment of the luteinizing hormone receptor causes familial male-limited precocious puberty. J Clin Endocrinol Metab 80:3168-3172
12. Laue L, Chan WY, Hsueh AJ, Kudo M, Hsu SY, Wu SM, Blomberg L, Cutler Jr GB 1995 Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty. Proc Natl Acad Sci USA 92:1906-1910
13. Yano K, Kohn LD, Saji M, Kataoka N, Okuno A, Cutler Jr GB 1996 A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene. Biochem Biophys Res Commun 220:1036-1042
14. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M 2000 Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289:739-745
15. Shenker A, Laue L, Kosugi S, Merendino Jr JJ, Minegishi T, Cutler Jr GB 1993 A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature 365:652-654
16. Charton M 1990 The quantitative description of amino acid, peptide, and protein properties and bioactivities. In: Taft RW, ed. Progress in physical organic chemistry. New York: Wiley; 163-284
17. Jones DT 1997 Progress in protein structure prediction. Curr Opin Struct Biol 7:377-387
18. Meng EC, Bourne H 2001 Receptor activation: what does rhodopsin structure tell us? Trends Pharmacol Sci 22:587-593
19. Schulz A, Schoneberg T, Paschke R, Schultz G, Gudermann T 1999 Role of the third intracellular loop for the activation of gonadotropin receptors. Mol Endocrinol 13:181-190
20. Kudo M, Osuga Y, Kobilka BK, Hsueh AJW 1996 Transmembrane regions V and VI of the human luteinizing hormone receptor are required for constitutive activation by a mutation in the third intracellular loop. J Biol Chem 271:22470-22478
21. Abell AN, McCormick DJ, Segaloff DL 1998 Certain activating mutations within helix 6 of the human luteinizing hormone receptor may be explained by alterations that allow transmembrane regions to activate Gs. Mol Endocrinol 12:1857-1869
22. Fritze O, Filipek S, Kuksa V, Palczewski K, Hofmann KP, Ernst OP 2003 Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation. Proc Natl Acad Sci USA 100:2290-2295
23. Martens JW, Verhoef-Post M, Abelin N, Ezabella M, Toledo SP, Brunner HG, Themmen APN 1998 A homozygous mutation in the luteinizing hormone receptor causes partial Leydig cell hypoplasia: correlation between receptor activity and phenotype. Mol Endocrinol 12:775-784
24. Green S, Issemann I, Sheer E 1988 A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res 16:369
25. Chen C, Okayama H 1987 High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7:2745-2752
26. Himmler A, Stratowa C, Czernilofsky AP 1993 Functional testing of human dopamine D1 and D5 receptors expressed in stable cAMP-responsive luciferase reporter cell lines. J Recept Res 13:79-94
27. Hall CV, Jacob PE, Ringold GM, Lee F 1983 Expression and regulation of Escherichia coli lacZ gene fusions in mammalian cells. J Mol Appl Genet 2:101-109
28. Blok LJ, Themmen APN, Peters AH, Trapman J, Baarends WM, Hoogerbrugge JW, Grootegoed JA 1992 Transcriptional regulation of androgen receptor gene expression in Sertoli cells and other cell types. Mol Cell Endocrinol 88:153-164
29. van Loenen HJ, Flinterman JF, Rommerts FFG 1994 High affinity FSH receptor binding is a slowly nonreversible process that appears not to be important for rapid receptor activation. Endocrine 2:1031-1035
30. 125I-labeled human follitropin. Biochim Biophys Acta 541:360-371
31. Xie YB, Wang H, Segaloff DL 1990 Extracellular domain of lutropin/choriogonadotropin receptor expressed in transfected cells binds choriogonadotropin with high affinity. J Biol Chem 265:21411-21414
32. Ji I, Ji TH 1991 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 128:2648-2650
33. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M 1983 Charmm: a program for macromolecular energy, minimization and dynamics calculations. J Comput Chem 4:187-217
34. Sali A, Blundell TL 1993 Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234:779-815