{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:18:49Z","timestamp":1784956729150,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,3,29]],"date-time":"2006-03-29T00:00:00Z","timestamp":1143590400000},"content-version":"vor","delay-in-days":118,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Of the 800\u2010900 genes in the human genome that appear to encode G\u2010protein\u2010coupled receptors (GPCRs), two are known to encode receptors that bind the three heterodimeric human gonadotropins, luteinizing hormone (LH), chorionic gonadotropin (CG), and follicle\u2010stimulating hormone (FSH). LH and CG bind to a common receptor, LHR, and FSH binds to a paralogous receptor. These GPCRs contain a relatively large ectodomain (ECD), responsible for high\u2010affinity ligand binding, and a transmembrane portion, as in the other GPCRs. The ECD contains nine leucine\u2010rich repeats capped by N\u2010terminal and C\u2010terminal cysteine\u2010rich regions. The overall goal of this research is to elucidate the molecular mechanisms by which CG and LH bind to and activate LHR and the latter, in turn, activates Gs\u03b1. A combination of molecular modeling and site\u2010directed mutagenesis, coupled with binding and signaling studies in transiently transfected HEK 293 cells expressing wild\u2010type and mutant forms of LHR, has been used to develop and test models for the LHR ECD, the CG\u2010LHR ECD complex, and the structural changes in the transmembrane helices and intracellular loops, particularly loop 2, that accompany receptor activation. In addition, a single\u2010chain CG\u2010LHR complex was designed in which a fusion protein of the two subunits of human CG was linked to full\u2010length LHR. This ligand\u2010receptor complex was shown to be constitutively active in cellular models and in transgenic mice, the latter of which exhibit precocious puberty. From a combination of molecular modeling, site\u2010directed mutagenesis, genetic\/protein engineering, and receptor characterization in cellular and animal models, considerable insight is being developed on the mechanisms of normal and aberrant activation of LHR.<\/jats:p>","DOI":"10.1196\/annals.1336.006","type":"journal-article","created":{"date-parts":[[2006,2,7]],"date-time":"2006-02-07T23:23:00Z","timestamp":1139354580000},"page":"41-54","source":"Crossref","is-referenced-by-count":25,"title":["Structure\u2010Function Relationships of the Luteinizing Hormone Receptor"],"prefix":"10.1111","volume":"1061","author":[{"given":"DAVID","family":"PUETT","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YONGSHENG","family":"LI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KRASSIMIRA","family":"ANGELOVA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GENEVA","family":"DEMARS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"THOMAS P.","family":"MEEHAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FRANCESCA","family":"FANELLI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PREMA","family":"NARAYAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,3,29]]},"reference":[{"key":"e_1_2_8_2_2","first-page":"1256","article-title":"The G\u2010protein\u2010coupled receptors in the human genome form five main families","volume":"63","author":"Fredriksson R.","year":"2003","journal-title":"Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol."},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/152165401753544214"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:18:3:285"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.2.0462"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2004.01.006"},{"key":"e_1_2_8_7_2","first-page":"30651","article-title":"Palmitoylation of luteinizing hormone\/human choriogonadotropin receptors in transfected cells","volume":"269","author":"Kawate N.","year":"1994","journal-title":"Abolition of palmitoylation by mutation of Cys-621 and Cys-622 residues in the cytoplasmic tail increases ligand-induced internalization of the receptor. J. Biol. Chem."},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.9.2.141"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1352(200009\/10)13:5<223::AID-JMR501>3.0.CO;2-L"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/369455a0"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00054-X"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2845"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.3.0603"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5480.739"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03206"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.10.9.1147"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.34.20020"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(01)00222-2"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(01)00272-6"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/366751a0"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzg081"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh034"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00232-0"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10396"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.107355"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(03)74020-8"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889891004399"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1203"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3516"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203272200"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0050"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2000-0026"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.30.17741"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105791200"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(97)04035-5"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.13.2.0233"},{"key":"e_1_2_8_37_2","doi-asserted-by":"crossref","first-page":"20970","DOI":"10.1016\/S0021-9258(17)45312-9","article-title":"Functional analysis of the cytoplasmic domains of the human thyrotropin receptor by site\u2010directed mutagenesis","volume":"265","author":"Chazenbalk G.D.","year":"1990","journal-title":"J. Biol. Chem."},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(01)00720-1"},{"key":"e_1_2_8_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10445"},{"key":"e_1_2_8_40_2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1210\/edrv.21.5.0409","article-title":"Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary\u2010gonadal function","volume":"21","author":"Themmen A.P.N.","year":"2000","journal-title":"Endocrine Rev."},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.49.31638"},{"key":"e_1_2_8_42_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.141.1.67"},{"key":"e_1_2_8_43_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01669"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/10606820212138"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0365"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1336.006","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1336.006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T01:01:30Z","timestamp":1695603690000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1336.006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,12]]}},"alternative-id":["10.1196\/annals.1336.006"],"URL":"https:\/\/doi.org\/10.1196\/annals.1336.006","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,12]]}}}