Department of Biology, York University, Toronto, Ontario, Canada.
PLoS One. 2013 Jun 14;8(6):e65605. doi: 10.1371/journal.pone.0065605. Print 2013.
AIDA1 links persistent chemical signaling events occurring at the neuronal synapse with global changes in gene expression. Consistent with its role as a scaffolding protein, AIDA1 is composed of several protein-protein interaction domains. Here we report the NMR structure of the carboxy terminally located phosphotyrosine binding domain (PTB) that is common to all AIDA1 splice variants. A comprehensive survey of peptides identified a consensus sequence around an NxxY motif that is shared by a number of related neuronal signaling proteins. Using peptide arrays and fluorescence based assays, we determined that the AIDA1 PTB domain binds amyloid protein precursor (APP) in a similar manner to the X11/Mint PTB domain, albeit at reduced affinity (∼10 µM) that may allow AIDA1 to effectively sample APP, as well as other protein partners in a variety of cellular contexts.
AIDA1 将神经元突触中持续发生的化学信号事件与基因表达的全局变化联系起来。与作为支架蛋白的作用一致，AIDA1 由几个蛋白-蛋白相互作用结构域组成。在这里，我们报告了羧基末端磷酸酪氨酸结合结构域（PTB）的 NMR 结构，该结构域存在于所有 AIDA1 剪接变体中。对肽的全面研究确定了一个 NxxY 基序周围的共识序列，该序列被许多相关的神经元信号蛋白共享。使用肽阵列和基于荧光的测定法，我们确定 AIDA1 PTB 结构域以类似于 X11/Mint PTB 结构域的方式结合淀粉样蛋白前体 (APP)，尽管亲和力降低（约 10 µM），这可能使 AIDA1 能够有效地对 APP 以及其他蛋白质伙伴进行采样在各种细胞环境中。
