手机知网 App
24小时专家级知识服务
打 开
手机知网|搜索

PDZ Domain-mediated Synaptic Signal Transduction Complex Organization

Hidehito Toehio

  Signal transmission in neurons is mediated by a wide variety of ion channels and receptors specifically localized at the synaptic membrane.Rather than freely diffusing in the membrane,these ion channels and receptors form multimeric clusters.A large class of PDZ(PSD-95,DLG,and ZO-1)domain containing proteins were identified to mediate targeting and clustering of channels,receptors,cell adhesion proteins,and other signaling enzymes at the specific sites of cell-cell contact,including synapse.A typical PDZ domain contains~90 amino acid residues,and binds specifically to a short peptide at the extreme carboxyl-end of target protein.In addition,PDZ domains can also bind to internal sequences,thereby forming PDZ/PDZ heterodimers.Our laboratory has made significant contributions in understanding structural basis of PDZ domain mediated protein-protein interactions.The solution structure of the extended nNOS PDZ domain complexed with an associated peptide solved in our laboratory showed,for the first time, how PDZ/PDZ hetero-dimer forms(1).Using nNOS PDZ and PSD-95 PDZ2 dimer complex as the model,we performed a series of studies in elucidating structural and biochemical basis of PDZ domain hetero-dimer formation(2,3).Recently,we turned our attentions to the novel biological functions observed in tandem PDZ repeats.For example, we showed that the PDZ domains of GRIP mutually chaperon each other,and such inter- domain chaperoning is essential for GRIP to interact with the AMPA receptor(4).I will present some of the details of PDZ-domain mediated protein-protein interaction studies using a combination of NMR and biochemical studies.……