title: Structural landscape of isolated agonist-binding domains from single AMPA receptors.
abstract: AMPA receptors mediate fast excitatory neurotransmission by converting chemical signals into electrical signals, and thus it is important to understand the relationship between their chemical biology and their function. We used single-molecule fluorescence resonance energy transfer to examine the conformations explored by the agonist-binding domain of the AMPA receptor for wild-type and T686S mutant proteins. Each form of the agonist binding domain showed a dynamic, multistate sequential equilibrium, which could be identified only using wavelet shrinkage, a signal processing technique that removes experimental shot noise. These results illustrate that the extent of activation depends not on a rigid closed cleft but instead on the probability that a given subunit will occupy a closed-cleft conformation, which in turn is determined not only by the lowest energy state but also by the range of states that the protein explores.
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas, USA. cflandes@rice.edu
authors.forename: Christy F
authors.initials: CF
authors.lastname: Landes
authors.forename: Anu
authors.initials: A
authors.lastname: Rambhadran
authors.forename: J Nick
authors.initials: JN
authors.lastname: Taylor
authors.forename: Ferandre
authors.initials: F
authors.lastname: Salatan
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Jayaraman
mesh_terms: D031541:Fluorescence Resonance Energy Transfer; D005971:Glutamates / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D018091:Receptors, AMPA / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005971:Glutamates; D050505:Mutant Proteins; D021122:Protein Subunits; D018091:Receptors, AMPA