Glutamate 301 of the mouse gonadotropin-releasing hormone receptor confers specificity for arginine 8 of mammalian gonadotropin-releasing hormone.

Flanagan, Colleen A.; Becker, I. I.; Davidson, James S.; Wakefield, I.; Zhou, Wei; Sealfon, Stuart C.; Millar, Robert P.

doi:10.1016/s0021-9258(17)31693-9

Cited by 125 publications

(47 citation statements)

References 30 publications

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“…value in the nanomolar range, comparable with the EC &! value of cGnRH-II for the catfish GnRH receptor [6,7].…”

Section: Discussionmentioning

confidence: 99%

“…The arginine residue on position 8 of mGnRH is necessary for the mouse GnRH receptor to bind mGnRH with high affinity [6].…”

Section: Activities Of Gnrh Analogues With and Without Argmentioning

confidence: 99%

“…For that reason, non-mammalian GnRH receptors were not expected to contain a negatively charged residue at the position similar to Glu$!" of the mouse GnRH receptor that confers the high affinity of the mouse receptor for [Arg)]GnRH ligands [6]. However, the catfish GnRH receptor contains an aspartic acid residue at position 304, similar to Glu$!"…”

Section: Asp 304 Of the Catfish Gnrh Receptor Mediates The Recognition Of [Arg 8 ]Gnrhs But Is Not Essential For The Recognition Of [Tyr mentioning

confidence: 99%

“…GnRH receptors belong to the family of rhodopsin-like Gprotein-coupled receptors (GPCRs). Previous studies have shown that mammalian GnRH receptors are selective for mammalian GnRH (mGnRH), but can also be substantially activated by cGnRH-II [6][7][8]. Non-mammalian GnRH receptors are promiscuous in interacting well with most of the vertebrate GnRHs but seem to have a preference for cGnRH-II [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that the negatively charged Glu$!" residue of the mouse GnRH receptor has a major role in the receptor recognition of the Arg) residue in mGnRH [6]. In this context it is intriguing that the catfish GnRH receptor contains a negatively charged Asp$!% residue at the position similar to Glu$!"…”

Section: Introductionmentioning

confidence: 99%

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Chimaeric gonadotropin-releasing hormone (GnRH) peptides with improved affinity for the catfish (Clarias gariepinus) GnRH receptor

Blomenröhr

Laak²,

Kühne³

et al. 2002

Biochem. J.

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The gonadotropin-releasing hormone (GnRH) receptor in catfish differs from its mammalian counterparts in showing a very low affinity for the hypothalamic GnRH form [i.e. catfish GnRH (cfGnRH)] and a very high affinity for the highly conserved mesencephalic GnRH, chicken GnRH-II (cGnRH-II). In the present study we investigated the molecular interactions between ligand and receptor involved in determining the ligand selectivity of the catfish GnRH receptor. Studies on the binding characteristics of the catfish GnRH receptor for cfGnRH and cGnRH-II as well as for mammalian GnRH (mGnRH) and synthetic chimaeric GnRHs, differing at positions 5, 7 and 8, revealed that the low affinity of the catfish receptor for cfGnRH can be improved by replacing Leu(7) by a tryptophan residue and/or Asn(8) by either a tyrosine or an arginine residue. Testing cfGnRH and cGnRH-II as well as mGnRH and the chimaeric GnRHs on Asp(304)-->Ala, Asp(304)-->Glu and Asp(304)-->Asn mutant catfish GnRH receptors revealed that Asp(304) of the catfish receptor mediates the recognition of Arg(8) in mGnRH, as well as in the chimaeric peptides [Arg(8)]cfGnRH and [Arg(8)]cGnRH-II, but seems to be less important for the recognition of Tyr(8) in cGnRH-II. On the basis of these results, a three-dimensional model for the binding of [Arg(8)]cGnRH-II to the catfish GnRH receptor is proposed.

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“…value in the nanomolar range, comparable with the EC &! value of cGnRH-II for the catfish GnRH receptor [6,7].…”

Section: Discussionmentioning

confidence: 99%

“…The arginine residue on position 8 of mGnRH is necessary for the mouse GnRH receptor to bind mGnRH with high affinity [6].…”

Section: Activities Of Gnrh Analogues With and Without Argmentioning

confidence: 99%

Section: Asp 304 Of the Catfish Gnrh Receptor Mediates The Recognition Of [Arg 8 ]Gnrhs But Is Not Essential For The Recognition Of [Tyr mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chimaeric gonadotropin-releasing hormone (GnRH) peptides with improved affinity for the catfish (Clarias gariepinus) GnRH receptor

Blomenröhr

Laak²,

Kühne³

et al. 2002

Biochem. J.

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Solvation in simulated annealing and high-temperature molecular dynamics of proteins: A restrained water droplet model

Sankararamakrishnan

Konvicka

Mehler

et al. 2000

Int. J. Quant. Chem.

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ABSTRACT:The use of explicit water molecules in simulations of protein systems in solution at high temperatures (e.g., in simulated annealing protocols) is complicated by the temperature-dependent changes in the physical properties of water. We propose a new protocol for such simulations based on a solvation model in which a spherical harmonic restraint is applied to a water shell surrounding the primary solvent sphere containing the polypeptide. The performance of different force constants, applied in water shells of different widths, was tested in simulations at temperatures ranging from 300 to 500 K. The best results were obtained when small force constants (0.0007-0.002 kcal/mol Å 2 ) were applied to 5-Å water shells surrounding the primary water sphere constructed to accommodate the solute and water at the appropriate density. With an atom-based 14-Å cut-off this solvation model reproduces structural and dynamic properties of water in the range of temperatures tested here. Thus, the internal pressure is very well maintained during cooling in simulated annealing protocols, and the small force constants eliminate the potential artifacts of the surface effects and prevent the water molecules from evaporating in simulations at high temperature. The restrained water droplet model described here is computationally more economical than periodic boundary conditions (PBC) and is preferable to the PBC method in which the size of the box has to be adjusted to maintain the experimental density if simulations are performed at different temperatures. Its application is illustrated in the study of the extracellular domain of the receptor protein for the gonadotropin releasing hormone (GnRH). This receptor belongs to the family of seven transmembrane domain proteins involved in signal transduction from the extracellular environment into the cell. The extracellular loops (ECLs) connecting the seven transmembrane (TM) domains are exposed to aqueous solvent and play a key role in binding GnRH to its receptor. The solvation model was used in a successful simulated * Dedicated to Prof. Michael Zerner on his 60th birthday. CCC 0020-7608 / 00 / 010174-13 SIMULATED ANNEALING AND HIGH-TEMPERATURE MOLECULAR DYNAMICS OF PROTEINSannealing protocol that explored the conformational space of the interacting ECLs. We show that the resulting secondary structure of ECL 3 is supported by experimental data and depends on hydrophobic interactions that appear only in an appropriate representation of the solvent but cannot be obtained from the commonly used simulations in vacuum with the solvent modeled solely through a dielectric constant.

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G Protein‐Coupled Receptors and the G Protein Family

Ulloa‐Aguirre

Conn

1998

Comprehensive Physiology

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The sections in this article are: Structure of G Protein‐Coupled Receptors General Features Ligand‐Binding Domain G Protein‐Coupling Domain The Heterotrimeric G‐Protein Family General Features G Protein‐Regulatory Cycle Structural and Functional Relationships of Gα‐Subunit Gβγ Structure and Function Regulatory Mechanisms Mechanisms that Regulate Receptor Function G Protein‐Mediated Regulatory Mechanisms

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Glutamate 301 of the mouse gonadotropin-releasing hormone receptor confers specificity for arginine 8 of mammalian gonadotropin-releasing hormone.

Cited by 125 publications

References 30 publications

Chimaeric gonadotropin-releasing hormone (GnRH) peptides with improved affinity for the catfish (Clarias gariepinus) GnRH receptor

Chimaeric gonadotropin-releasing hormone (GnRH) peptides with improved affinity for the catfish (Clarias gariepinus) GnRH receptor

Solvation in simulated annealing and high-temperature molecular dynamics of proteins: A restrained water droplet model

G Protein‐Coupled Receptors and the G Protein Family

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