26 research outputs found
Glutamate receptors as seen by light: spectroscopic studies of structure-function relationships
Allosteric mechanism in AMPA receptors: A FRET-based investigation of conformational changes
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are the primary mediators of fast excitatory synaptic transmission in the mammalian CNS. Structures of the extracellular ligand-binding domain suggest that the extent of cleft closure in the ligand-binding domain controls the extent of activation of the receptor. Here we have developed a fluorescence resonance energy transfer-based probe that allows us to study the extent of cleft closure in the isolated ligand-binding domain in solution. These investigations show that the wild-type protein exhibits a graded cleft closure that correlates to the extent of activation, which is in qualitative agreement with the crystal structures. However, the changes in extent of cleft closure between the apo and agonist-bound states are smaller than that observed in the crystal structures. We have also used this method to study the L650T mutant and show that in solution the α-amino-5-methyl-3-hydroxy-4-isoxazole propionate-bound form of this mutant exists primarily in a conformation that is more closed than predicted based on the activity, indicating that the degree of cleft closure alone cannot be used as a measure of extent of activation of the receptor, and there are possibly other mechanisms in addition to cleft closure that mediate the subtleties in extent of activation by a given agonist
Luxation congénitale du genou à la naissance. Première partie : sémiologie clinique et classification
Luxation congénitale du genou à la naissance. Seconde partie : pertinence d’une nouvelle classification sur les orientations thérapeutiques, les résultats et les facteurs pronostiques
Congenital dislocation of the knee at birth – Part 2: Impact of a new classification on treatment strategies, results and prognostic factors
Fluorocarbon-peptide conjugates (FPC): new concept to increase the metabolic stability of peptides for therapeutic applications
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