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How the G protein-coupled receptor activates GTP-binding protein

The Pharmacogenomics Journal volume 1, pages 225–228 (2001)Cite this article

In the post-genomic era, whole genome sequences from various organisms including a draft sequence of the human genome are available. The most surprising result of human genome sequencing is that only 30 000 genes are expected.1 More than 600 family members were identified as G protein-coupled receptors (GPCR) or seven-transmembrane receptors (7TMR). 7TMRs are the major targets for developing therapeutics because of the significance and variation of biological function including vision, odor, taste, inflammation, neurotransmission and chemotactics.2 Thus it is responsible for many disease symptoms including pain, fever, allergy, mental disorder, even AIDS.

The molecular mechanism of 7TMRs is a switch for cellular signal transduction by extra-cellular signals including light, odorant chemicals, hormones, neurotransmitters and chemokines via GTP binding-protein (G protein) activation. The biggest super family of proteins, 7TMRs, consist of three families including rhodopsin, secretin and metabotropic glutamate receptor classes. The super family characterizes the structure of the seven trans-membrane helical bundle, and the dominant rhodopsin family shares several highly conserved amino acid residues despite their diverse sequences.3 In contrast to 7TMRs, G proteins as the corresponding counterparts were identified less than one twentieth as often as 7TMRs.1 Therefore it has been thought that the molecular mechanism of 7TMR activation is also common. Now the atomic structure of a representative 7TMR rhodopsin4 has become available, accompanied by versatile biochemical studies on 7TMRs including Khorana's systematic mutation studies of rhodopsin,5,6 and many G protein structures including complex forms and valuable G protein mutants.7 And now we can add new Gα mutants, which are activated only by Gβγ without an activated receptor, according to a receptor-activating hypothesis by Rondard et al.8

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Acknowledgements

I am grateful to many people including members of my laboratory for stimulating discussions.

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  1. Structural Biophysics Laboratory, RIKEN Harima Institute, Mikazuki, Sayo, Hyogo, Japan

    M Miyano

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Correspondence to M Miyano.

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Miyano, M. How the G protein-coupled receptor activates GTP-binding protein. Pharmacogenomics J 1, 225–228 (2001). https://doi.org/10.1038/sj.tpj.6500034

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