Superfamily of G-protein coupled receptors (GPCRs) – extraordinary and outstanding success of evolution
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2014, Vol 68, Issue
Abstract
The G protein-coupled receptors (GPCRs) are considered as very diverse and also surprisingly successful structures during the whole evolutionary process, being capable of transducing the different forms of “information” within the cell and also between cells, such as different peptides, lipids, proteins, nucleotides, nucleosides, organic odorants and photons. Complex studies as well as two-dimensional crystallization of rhodopsin, their paradigm, led to the creation of a useful model having a common central core, consisting of seven transmembrane helical domains, which undergoes appropriate structural modification during activation and signal transduction. After the complete delineation of the human genome, which is the apogee of human scientific civilization and culture, it was possible to identify more than 800 human GPCR sequences and in parallel analyze 342 unique functional nonolfactory human GPCR sequences with phylogenetic analyses. These results support, with high bootstrap values, the existence of five main families, named by the authors glutamate, rhodopsin, adhesion, frizzle/taste2, and secretin, forming the GRAFS classification system. Positions of the GPCRs in chromosomal paralogous regions indicate the importance of tetraploidizations or local gene duplication events during their creation. Some families of GPCRs show, however, very little or no similarity in the sequence of amino acid chains. They utilize an enormous number of different domains to bind ligands and to activate the appropriate G-proteins. The delicate tuning of their coupling to G proteins is further regulated by splicing, RNA editing and phosphorylation. A number of GPCRs may also form homodimers or heterodimers with structurally different GPCRs and also with membrane-bound proteins having one transmembrane domain. It should also be stressed that not all GPCRs are strictly faithful to G proteins because growing evidence indicates that they can interact directly, via their C-terminal domain, with proteins containing PDZ domains, which are present in the PDZ proteins. These proteins organize the NMDA receptors and some K+ channels while their PDZ domains generally bind 3-4 amino-acid stretches of C-terminal sequences of target proteins. The -S/TXV motif was found in some PDZ target proteins. GPCRs can also interact with the Enabled/VASP homology (EVH)-like domain which interacts directly with group 1 mGluR receptors. Every year brings new very important data in research of these proteins, which should be called “the most successful structures evolved during the whole of animal evolution”.
Authors and Affiliations
Kazimierz Kochman
Keywords
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