Department of Chemistry, Rice University, Houston, Texas, USA.
Nat Chem Biol. 2011 Mar;7(3):168-73. doi: 10.1038/nchembio.523. Epub 2011 Feb 6.
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.
AMPA 受体将化学信号转化为电信号，从而介导快速的兴奋性神经递质传递，因此了解其化学生物学与其功能之间的关系非常重要。我们使用单分子荧光共振能量转移技术来研究 AMPA 受体激动剂结合域在野生型和 T686S 突变蛋白中的构象。激动剂结合域的每种形式都表现出一种动态的、多态的顺序平衡，只有使用小波收缩这种信号处理技术才能识别出来，该技术可以去除实验中的随机噪声。这些结果表明，激活的程度不仅取决于刚性的闭合裂隙，还取决于给定亚基占据闭合裂隙构象的概率，而这反过来又不仅取决于最低能量状态，还取决于蛋白质所探索的状态范围。
