Interesting Structural and Dynamical Behaviors Exhibited by the AF-6 PDZ Domain upon Bcr Peptide Binding

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• 作者：Xiaogang Niu ; Quan Chen ; Jiahai Zhang ; Weiqun Shen ; Yunyu Shi ; Jihui Wu
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：December 25, 2007
• 年：2007
• 卷：46
• 期：51
• 页码：15042 - 15053
• 全文大小：534K
• 年卷期：v.46,no.51(December 25, 2007)
• ISSN：1520-4995

文摘

PDZ (postsynaptic density-95, disks large, zonula occludens-1) domains are small, protein-protein interaction modules that have multiple binding surfaces for the docking of diverse molecules.These domains can propagate signals from ligand-binding site to distal regions of the structure throughallosteric communication. Recent works have revealed that picosecond to nanosecond time scale dynamicsplay a potential role in propagating long-range signals within a protein. Comparison of AF-6 PDZ domainstructures in free and complex forms shows a conformation rearrangement of distal surface 2, which isfar from the peptide binding groove. The relaxation dispersion experiments detected that the free AF-6PDZ domain was sampling multiple conformations; millisecond dynamics mapped a network for allosterysignal transmission throughout the AF-6 PDZ domain in the weak saturation state, and intramolecularmotions were observed in distal surface 1 when the protein was saturated. These results provide evidencethat the allosteric process in the AF-6 PDZ domain is not two-state; instead, the millisecond dynamicnetwork provides a mechanism for the transmission of allosteric signals throughout a protein. Interestingly,the two distal surfaces of the AF-6 PDZ domain respond differently to peptide binding; distal surface 1changes in millisecond dynamics, whereas distal surface 2 undergoes structural rearrangement. Thesignificance of the different response patterns in the signaling pathway and its relevance to the functionof the AF-6 PDZ domain should be studied further.