A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function
Publication in refereed journal

香港中文大學研究人員

引用次數
Scopus ( 14/10/2020)
替代計量分析
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其它資訊
摘要Shank and SAPAP (synapse-associated protein 90/postsynaptic density-95-associated protein) are two highly abundant scaffold proteins that directly interact with each other to regulate excitatory synapse development and plasticity. Mutations of SAPAP, but not other reported Shank PDZ domain binders, share a significant overlap on behavioral abnormalities with the mutations of Shank both in patients and in animal models. The molecular mechanism governing the exquisite specificity of the Shank/SAPAP interaction is not clear, however. Here we report that a sequence preceding the canonical PDZ domain of Shank, together with the elongated PDZ BC loop, form another binding site for a sequence upstream of the SAPAP PDZ-binding motif, leading to a several hundred-fold increase in the affinity of the Shank/SAPAP interaction. We provide evidence that the specific interaction afforded by this newly identified site is required for Shank synaptic targeting and the Shank-induced synaptic activity increase. Our study provides a molecular explanation of how Shank and SAPAP dosage changes due to their gene copy number variations can contribute to different psychiatric disorders.
著者Zeng ML, Shang Y, Guo TF, He QH, Yung WH, Liu K, Zhang MJ
期刊名稱Proceedings of the National Academy of Sciences
出版年份2016
月份5
日期31
卷號113
期次22
出版社NATL ACAD SCIENCES
頁次E3081 - E3090
國際標準期刊號0027-8424
語言英式英語
關鍵詞PDZ; SAPAP; Shank; specific interaction; synapse
Web of Science 學科類別Multidisciplinary Sciences; Science & Technology - Other Topics

上次更新時間 2020-15-10 於 02:34