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Chapitre D'ouvrage Année : 1993

Bioamine receptors: Evolutionary and functional variations of a structural leitmotiv

Résumé

Bioamines act as neurohormonal messengers through their binding to receptors which belong to the largest membrane protein family known so far: the seven spanning membrane receptors. This class of receptors transmits the effect of agonist binding to intracellular effectors by interacting with an intermediary G-protein. The diversity of receptor subtypes inside the protein family, observed in many animal species, is the result of a long evolutionary process. The tendency to protein diversification depends upon gene duplications and upon the continuous accumulation of mutations. The maintenance of vital functions in organisms, however, strictly requires enough structural conservation to ensure the functionality of the corresponding proteins. Both forces cooperate to ensure the adaptation of organisms to a changing environment. We have reviewed here the main conformational and functional constraints exerted on the structure of the bioamine receptors. They are mainly the transmembrane conformation of the receptors, their ability to bind ligands, to interact with G-proteins and to desensitize. The molecular basis of the biochemical and pharmacological differences used to classify the members of the receptor family have also been examined. Interestingly, this classification is very close to that obtained by the molecular phylogeny methods, used to elucidate the evolutionary relationships between bioamine receptors. However, this latter classification allows to accurately distinguish between different receptor subtypes (paralogous genes) and species homologous (orthologous genes). In addition, the calculation of phylogenetical distances reveals two main periods of diversification: the first one occurred before the separation of arthropods from vertebrates, in the Precambrian, and corresponds to the appearance of the main subtypes of the bioamine receptors. The second one, which occurred about 400 million years ago, might accompany the cephalization of the CNS in vertebrates.
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Dates et versions

hal-03576976 , version 1 (16-02-2022)

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Philippe Vernier, Hervé Philippe, Philippe Samama, Jacques Mallet. Bioamine receptors: Evolutionary and functional variations of a structural leitmotiv. Comparative Molecular Neurobiology, 63, Birkhäuser Basel, pp.297-337, 1993, ⟨10.1007/978-3-0348-7265-2_17⟩. ⟨hal-03576976⟩

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