Common structural requirements for heptahelical domain function in class A and class C GPCRS.

@article{citeulike:1122351, abstract = {G protein-coupled receptors (GPCRs) are key players in cell communication. Several classes of such receptors have been identified. Although all GPCRs possess a heptahelical domain directly activating G proteins, important structural and sequence differences within receptors from different classes suggested distinct activation mechanisms. Here we show that highly conserved charged residues likely involved in an interaction network between transmembrane domains (TM) 3 and 6 at the cytoplasmic side of class C GPCRs are critical for activation of the GABAB receptor. Indeed, the loss of function resulting from the mutation of the conserved lysine residue into aspartate or glutamate in the TM3 of GABAB2 can be partly rescued by mutating the conserved acidic residue of TM6 into either lysine or arginine. In addition, mutation of the conserved lysine into an acidic residue leads to a non-functionnal receptor that displays a high agonist affinity. This is reminiscent to a similar ionic network that constitutes a lock stabilizing the inactive state of many class A rhodopsin-like GPCRs. These data reveal that despite their original structure class C GPCRs share with class A receptors at least some common structural feature controlling G-protein activation.}, address = {Pharmacology, IGF - Institut de Genomique Fonctionnelle, Montpellier cedex 5 34094.}, author = {Binet, Virginie and Duthey, B\'{e}atrice and Lecaillon, Jennifer and Vol, Claire and Quoyer, Julie and Labesse, Gilles and Pin, Jean-Philippe P. and Pr\'{e}zeau, Laurent }, citeulike-article-id = {1122351}, doi = {http://dx.doi.org/10.1074/jbc.M611071200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {activation, class\_c, gaba, gpcr, switch}, month = {February}, posted-at = {2007-02-26 09:21:25}, priority = {2}, title = {Common structural requirements for heptahelical domain function in class A and class C GPCRS.}, url = {http://dx.doi.org/10.1074/jbc.M611071200}, year = {2007} }

TY - JOUR ID - citeulike:1122351 L3 - citeulike-article-id:1122351 TI - Common structural requirements for heptahelical domain function in class A and class C GPCRS. JF - J Biol Chem AD - Pharmacology, IGF - Institut de Genomique Fonctionnelle, Montpellier cedex 5 34094. SN - 0021-9258 N2 - G protein-coupled receptors (GPCRs) are key players in cell communication. Several classes of such receptors have been identified. Although all GPCRs possess a heptahelical domain directly activating G proteins, important structural and sequence differences within receptors from different classes suggested distinct activation mechanisms. Here we show that highly conserved charged residues likely involved in an interaction network between transmembrane domains (TM) 3 and 6 at the cytoplasmic side of class C GPCRs are critical for activation of the GABAB receptor. Indeed, the loss of function resulting from the mutation of the conserved lysine residue into aspartate or glutamate in the TM3 of GABAB2 can be partly rescued by mutating the conserved acidic residue of TM6 into either lysine or arginine. In addition, mutation of the conserved lysine into an acidic residue leads to a non-functionnal receptor that displays a high agonist affinity. This is reminiscent to a similar ionic network that constitutes a lock stabilizing the inactive state of many class A rhodopsin-like GPCRs. These data reveal that despite their original structure class C GPCRs share with class A receptors at least some common structural feature controlling G-protein activation. KW - activation KW - class_c KW - gaba KW - gpcr KW - switch AU - Binet, Virginie AU - Duthey, Béatrice AU - Lecaillon, Jennifer AU - Vol, Claire AU - Quoyer, Julie AU - Labesse, Gilles AU - Pin, Jean-Philippe AU - Prézeau, Laurent PY - 2007/02/19/ UR - http://dx.doi.org/10.1074/jbc.M611071200 ER -