A model for the functioning of family 3 GPCRs

被引：97

作者：

Parmentier, ML ^{[1
]}

Prézeau, L ^{[1
]}

Bockaert, J ^{[1
]}

Pin, JP ^{[1
]}

机构：

[1] CNRS, UPR 9023, F-34094 Montpellier 5, France

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2002年 / 23卷 / 06期

关键词：

D O I：

10.1016/S0165-6147(02)02016-3

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Family 3 G-protein-coupled receptors (GPCRs) comprise the metabotropic glutamate (mglu) receptors, GABA(B) receptors, Ca2+-sensing receptors and some taste and putative pheromone receptors. All are composed of two domains, an extracellular ligand-binding domain and a transmembrane heptahelical domain that activates G proteins. Here we propose a model for the function of family 3 GPCRs that takes into account their structure. This model fits with specific pharmacological features of some family 3 GPCRs, such as modulation by positive and negative allosteric regulators. The model also reveals differences between GABA(B) receptors and Group I mglu receptors: in the former there is 'tight' functional coupling between the two domains of the receptor whereas the 'loose' coupling in the latter gives these receptors specific features not shared by many other GPCRs.

引用

收藏

页码：268 / 274

页数：7

相关论文

共 40 条

[1] Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer [J].

Ango, F ;

Prézeau, L ;

Muller, T ;

Tu, JC ;

Xiao, B ;

Worley, PF ;

Pin, JP ;

Bockaert, J ;

Fagni, L .

NATURE, 2001, 411 (6840) :962-965

[2] Intermolecular interactions between dimeric calcium-sensing receptor monomers are important for its normal function [J].

Bai, M ;

Trivedi, S ;

Kifor, O ;

Quinn, SJ ;

Brown, EM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :2834-2839

[3] Three-dimensional model of the extracellular domain of the type 4a metabotropic glutamate receptor. New insights into the activation process [J].

Bessis, AS ;

Bertrand, HO ;

Galvez, T ;

De Colle, C ;

Pin, JP ;

Acher, F .

PROTEIN SCIENCE, 2000, 9 (11) :2200-2209

[4] Molecular tinkering of G protein-coupled receptors: an evolutionary success [J].

Bockaert, J ;

Pin, JP .

EMBO JOURNAL, 1999, 18 (07) :1723-1729

[5] Pharmacology of muscarinic receptor subtypes constitutively activated by G proteins [J].

Burstein, ES ;

Spalding, TA ;

Brann, MR .

MOLECULAR PHARMACOLOGY, 1997, 51 (02) :312-319

[6] BAY36-7620:: A potent non-competitive mGlu1 receptor antagonist with inverse agonist activity. [J].

Carroll, FY ;

Stolle, A ;

Beart, PM ;

Voerste, A ;

Brabet, I ;

Mauler, F ;

Joly, C ;

Antonicek, H ;

Bockaert, J ;

Müller, T ;

Pin, JP ;

Prézau, L .

MOLECULAR PHARMACOLOGY, 2001, 59 (05) :965-973

[7] Characterization of [3H]-(2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine ([3H]-DCG IV) binding to metabotropic mGlu2 receptor-transfected cell membranes [J].

Cartmell, J ;

Adam, G ;

Chaboz, S ;

Henningsen, R ;

Kemp, JA ;

Klingelschmidt, A ;

Metzler, V ;

Monsma, F ;

Schaffhauser, H ;

Wichmann, J ;

Mutel, V .

BRITISH JOURNAL OF PHARMACOLOGY, 1998, 123 (03) :497-504

[8]

CHIDIAC P, 1994, MOL PHARMACOL, V45, P490

[9] Pharmacological properties of 5-hydroxytryptamine4 receptor antagonists on constitutively active wild-type and mutated receptors [J].

Claeysen, S ;

Sebben, M ;

Bécamel, C ;

Eglen, RM ;

Clark, RD ;

Bockaert, J ;

Dumuis, A .

MOLECULAR PHARMACOLOGY, 2000, 58 (01) :136-144

[10] Modeling of amino-terminal domains of group I metabotropic glutamate receptors: Structural motifs affecting ligand selectivity [J].

Costantino, G ;

Macchiarulo, A ;

Pellicciari, R .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (26) :5390-5401

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