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Conformational change of the transmembrane helices II and IV of metabotropic glutamate receptor involved in G protein activation
Author(s) -
Yamashita Takahiro,
Terakita Akihisa,
Kai Toshihiro,
Shichida Yoshinori
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05443.x
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 4 , metabotropic glutamate receptor 2 , metabotropic glutamate receptor 6 , transmembrane domain , metabotropic glutamate receptor 1 , metabotropic receptor , metabotropic glutamate receptor 5 , chemistry , glutamate receptor , metabotropic glutamate receptor 3 , metabotropic glutamate receptor 8 , transmembrane protein , neuroscience , biophysics , receptor , biochemistry , biology
G protein‐coupled receptors are classified into several families on the basis of their amino acid sequences and the members of the same family exhibit sequence similarity but those of different families do not. In family 1 GPCRs such as rhodopsin and adrenergic receptor, extensive studies have revealed the stimulus‐dependent conformational change of the receptor: the rearrangement of transmembrane helices III and VI is essential for G protein activation. In contrast, in family 3 GPCRs such as metabotropic glutamate receptor (mGluR), the inter‐protomer relocation upon ligand binding has been observed but there is much less information about the structural changes of the transmsmbrane helices and the cytoplasmic domains. Here we identified constitutively active mutation sites at the cytoplasmic borders of helices II and IV of mGluR8 and successfully inhibited the G protein activation ability by engineering disulfide cross‐linking between these cytoplasmic regions. The analysis of all possible single substitution mutants of these residues revealed that some steric interactions around these sites would be important to keep the receptor protein inactive. These results provided the model that the conformational changes at the cytoplasmic ends of helices II and IV of mGluR are involved in the efficient G protein coupling.