Purification and Structural Analysis of a Soluble Human Chorionogonadotropin Hormone-Receptor Complex

Rémy, Jean-Serge; Nespoulous, Claude; Grosclaude, Jeanne; Grebert, Denise; Couture, Laurence; Pajot, Edith; Salesse, Roland

doi:10.1074/jbc.m005206200

Cited by 45 publications

(22 citation statements)

References 37 publications

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“…Other examples in which the N-terminal domain of a GPCR binds ligand are the metabotropic glutamate receptor (33,34,51), the luteinizing hormone/human chorionic gonadotropin receptor (29), the follicle stimulating hormone receptor (28), the pituitary adenylate cyclase-activating polypeptide receptor (52), the PTH receptor (31), and the glucagon-like peptide-1 receptor (32), the last two also being members of the receptor subfamily to which the CRF receptor belongs. The glucagonlike peptide-1R, expressed and purified as a soluble protein in Chinese hamster lymphoblastoma cells, exhibited lower binding affinity compared with the native receptor, and lost activity after reduction of the disulfide bonds (32).…”

Section: Discussionmentioning

confidence: 99%

“…Biochemical characterizations of soluble ECD-1s include those of receptors for follicle stimulating hormone (28), luteinizing hormone/human chorionic gonadotropin (29), calcium (30), PTH (31), glucagon-like peptide-1 (32), and glutamate (33). The ECD-1 of the metabotropic glutamate receptor has also been characterized structurally by x-ray crystallography to 2.2-Å resolution (34).…”

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confidence: 99%

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Expression, Purification, and Characterization of a Soluble Form of the First Extracellular Domain of the Human Type 1 Corticotropin Releasing Factor Receptor

Perrin¹,

Fischer²,

Kunitake³

et al. 2001

Journal of Biological Chemistry

108

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Corticotropin releasing factor (CRF), 1 a 41-amino acid peptide, was identified initially on the basis of its primary role in the activation of the hypothalamic-pituitary-adrenal in response to stress. The CRF family of ligands includes sauvagine from frog and urotensin from fish as well as the additional mammalian family members, urocortin (1, 2), urocortin II (3, 4), and urocortin III (4, 5). Broader roles for CRF and its ligand family now involve effects on the cardiovascular, reproductive, gastrointestinal, immune, and central nervous systems (6 -8).The action of CRF and related ligands is initiated by binding to their receptors, which transduce an increase in intracellular cAMP. Thus far, two receptors, CRFR1 and CRFR2, have been cloned in mammals (9 -15). Homologous receptors have been identified in chicken (16), fish (17), and Xenopus (18) and a third receptor, CRFR3, with high levels of sequence identity to CRFR1, has recently been cloned in catfish (17). Both CRFR1 and CRFR2 exist as multiple splice variants and belong to the type B 7-transmembrane receptor family that includes receptors for growth hormone releasing factor, secretin, calcitonin, vasoactive intestinal peptide, glucagon, glucagon-like peptide, and parathyroid hormone (PTH). Receptors for the CRF ligand family have been characterized in the central nervous system, pituitary, gastrointestinal tract, epididymis, heart, gonads, and adrenals (6).The affinities of CRF and urocortin in binding to CRFR1 are nearly the same but in binding to CRFR2, urocortin is ϳ10 times more potent than CRF (19). Both urocortins II and III are highly selective in binding and activating CRFR2 compared with CRFR1 (4, 5). A synthetic peptide antagonist, astressin, binds with equally high affinity to CRFR1 and CRFR2 (19,20).The CRF receptor family consists of proteins with a relatively large first extracellular domain (ECD-1). Mutagenesis studies have identified regions of the CRF receptors that are implicated in differential recognition of agonists and antagonists, as well as in governing the ligand selectivity of the two types of receptors (21-25). We showed that a chimeric receptor in which the ECD-1 of CRFR1 replaced the ECD of the activin receptor, a single transmembrane receptor kinase (26), was capable of high affinity binding to both astressin and urocortin (21). The mode of receptor activation was explored by our study of a tethered peptide-receptor chimera in which the first 16 amino acids of CRF were substituted for the ECD-1 of CRFR1 (CRF (1-16)/R1 ⌬N ) (27). This chimera displayed continual signaling suggesting that the N-terminal third of CRF, when presented in proximity to the receptor, is able to cause activation.Biochemical characterizations of soluble ECD-1s include those of receptors for follicle stimulating hormone (28), luteinizing hormone/human chorionic gonadotropin (29), calcium (30), PTH (31), glucagon-like peptide-1 (32), and glutamate (33). The ECD-1 of the metabotropic glutamate receptor has

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Expression, Purification, and Characterization of a Soluble Form of the First Extracellular Domain of the Human Type 1 Corticotropin Releasing Factor Receptor

Perrin¹,

Fischer²,

Kunitake³

et al. 2001

Journal of Biological Chemistry

108

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“…In addition, it has convincingly been demonstrated that purified ectodomains, truncated from their serpentine domains, do bind their cognate hormones with high affinity (Cornelis et al 2001, Remy et al 2001, Schmidt et al 2001. Very recently, crystallization of a complex between FSH and the ectodomain of the FSHR has provided the first direct structural evidence for the residues implicated in recognition specificity at the atomic level of resolution (Fan & Hendrickson 2005).…”

Section: The Binding Specificity Of Gphrs Is Clearly Encoded In Theirmentioning

confidence: 99%

Specificity and promiscuity of gonadotropin receptors

Costagliola

Urizar²,

Mendive³

et al. 2005

Reproduction

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The dichotomy between hormone recognition by the ectodomain and activation of the G protein by the rhodopsin-like serpentine portion is a well established property of glycoprotein hormone receptors. The specificity barrier avoiding promiscuous activation of the FSH receptor by the high concentration of human chorionic gonadotropin (hCG) prevailing during human pregnancy was thus believed to lie in the ectodomain. In the past two years, mutations responsible for rare spontaneous cases of ovarian hyperstimulation syndromes have partially modified this simple view. Five naturally occurring mutations have been identified which cause an increase in the sensitivity of the FSH receptor to hCG. Surprisingly, these mutations are all located in the serpentine portion of the receptor. In addition to their effect on sensitivity to hCG, they increase sensitivity of the FSH receptor to TSH, and are responsible for activating the receptor constitutively. Together, the available information indicates that the ectodomain and the serpentine domain of the FSH receptor each contribute to the specificity barrier preventing its spurious activation by hCG. While the former is responsible for establishment of binding specificity, the latter introduces a novel notion of functional specificity. Recent data demonstrate that LH and FSH receptors can constitute functional homo-and heterodimers. This suggests the possibility that in cells co-expressing the two receptors, such as granulosa cells, the heterodimers might be endowed with functional characteristics different from those of each homodimer.

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“…These receptors have a rhodopsinlike transmembrane (TM) domain (Palczewski et al 2000, Themmen & Huhtaniemi 2000, Dias & Van Roey 2001, Ascoli et al 2002, Szkudlinski et al 2002 in common with the superfamily of GPCRs. In addition, they have a large N-terminal extracellular domain (ECD; 359-414 amino acid residues; homology , 40%), which conveys specific hormone binding to the receptors (Braun et al 1991, Cornelis et al 2001, Remy et al 2001. The TMs of individual glycoprotein hormone receptors appear to be functionally interchangeable and display high sequence homology (, 70%) between the different glycoprotein hormone receptors.…”

Section: Gonadotrophin Receptorsmentioning

confidence: 99%

An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms

Themmen¹

2005

Reproduction

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New information about mutations and polymorphisms in the genes for the gonadotrophins and their receptors has become available in the last few years. In this short review mutations and polymorphisms in gonadotrophins, their receptors and their patho-physiological effects and implications are discussed. An increasingly clear picture about the structure -function relationships of gonadotrophin action is emerging from the combining the types and the locations of the mutations with their phenotypic effects and the information about the crystal structure of these molecules.

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Purification and Structural Analysis of a Soluble Human Chorionogonadotropin Hormone-Receptor Complex

Cited by 45 publications

References 37 publications

Expression, Purification, and Characterization of a Soluble Form of the First Extracellular Domain of the Human Type 1 Corticotropin Releasing Factor Receptor

Expression, Purification, and Characterization of a Soluble Form of the First Extracellular Domain of the Human Type 1 Corticotropin Releasing Factor Receptor

Specificity and promiscuity of gonadotropin receptors

An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms

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