title: Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels.
abstract: Glutamate is an indispensable neurotransmitter, triggering postsynaptic signals upon recognition by postsynaptic receptors. We questioned the phylogenetic position and the molecular details of when and where glutamate recognition arose in the glutamate-gated chloride channels. Experiments revealed that glutamate recognition requires an arginine residue in the base of the binding site, which originated at least three distinct times according to phylogenetic analysis. Most remarkably, the arginine emerged on the principal face of the binding site in the Lophotrochozoan lineage, but 65 amino acids upstream, on the complementary face, in the Ecdysozoan lineage. This combined experimental and computational approach throws new light on the evolution of synaptic signalling.
authors.affiliation: Neurophysiology and Neurosensory Systems, Technical University of Darmstadt, Darmstadt 64287, Germany.
authors.forename: Timothy
authors.initials: T
authors.lastname: Lynagh
authors.affiliation: Institute of Parasitology, McGill University, Macdonald Campus, St Anne-de-Bellevue, QC, Canada.
authors.forename: Robin N
authors.initials: RN
authors.lastname: Beech
authors.affiliation: Neurophysiology and Neurosensory Systems, Technical University of Darmstadt, Darmstadt 64287, Germany.
authors.forename: Maryline J
authors.initials: MJ
authors.lastname: Lalande
authors.affiliation: Neurophysiology and Neurosensory Systems, Technical University of Darmstadt, Darmstadt 64287, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Keller
authors.affiliation: Health Innovations Research Institute, School of Medical Sciences, RMIT University, Bundoora, VIC, Australia.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Cromer
authors.affiliation: Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Wolstenholme
authors.affiliation: Neurophysiology and Neurosensory Systems, Technical University of Darmstadt, Darmstadt 64287, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Laube
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D018118:Chloride Channels / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D018118:Chloride Channels; C109777:glutamate-gated chloride channels; D018698:Glutamic Acid; D001120:Arginine