Solution structure of the RIM1 α PDZ domain in complex with an ELKS1 b C-terminal peptide
Solution structure of the RIM1 α PDZ domain in complex with an ELKS1 b C-terminal peptide
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DOI：
10.1016/j.jmb.2005.07.047
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发表时间：
2005-09-16
影响因子：
5.6
通讯作者：
Rizo, J
中科院分区：
文献类型：
--
作者：
Lu, J;Li, HM;Rizo, J
PDZ结构域是广泛存在的蛋白质模块，通常识别靶蛋白的C-末端序列并帮助组织大分子信号复合物。这些序列通常以延伸的构象结合到在相应的PDZ结构域中的β-链和α-螺旋之间形成的相对浅的凹槽。由于这种结合模式，许多PDZ结构域主要识别靶蛋白的C-末端和倒数第二个侧链，其通常符合已被分类为不同类别的基序。然而，已经发现越来越多的PDZ结构域表现出不寻常的特异性。这些包括RIM的PDZ结构域，RIM是调节神经递质释放并帮助组织突触前活动区的大型多结构域蛋白质。RIM PDZ结构域以独特的特异性结合ELKS的C末端序列，该特异性涉及四个ELKS C末端残基中的每一个。为了阐明这种特异性的结构基础，我们使用NMR光谱法确定了RIM/ELKS C-末端肽复合物溶液中的3D结构。该结构表明，RIM PDZ结构域包含一个异常深而窄的肽结合沟，其具有与四个ELKS C-末端残基在其结合构象中互补的精致形状。该沟部分地由一组侧链形成，所述侧链在RIM PDZ结构域中选择性地保守，并且因此至少部分地决定其独特的特异性。(c)2005爱思唯尔有限公司保留所有权利。
PDZ domains are widespread protein modules that commonly recognize C-terminal sequences of target proteins and help to organize macromolecular signaling complexes. These sequences usually bind in an extended conformation to relatively shallow grooves formed between a beta-strand and an alpha-helix in the corresponding PDZ domains. Because of this binding mode, many PDZ domains recognize primarily the C-terminal and the antepenultimate side-chains of the target protein, which commonly conform to motifs that have been categorized into different classes. However, an increasing number of PDZ domains have been found to exhibit unusual specificities. These include the PDZ domain of RIMs, which are large multidomain proteins that regulate neurotransmitter release and help to organize presynaptic active zones. The RIM PDZ domain binds to the C-terminal sequence of ELKS with a unique specificity that involves each of the four ELKS C-terminal residues. To elucidate the structural basis for this specificity, we have determined the 3D structure in solution of an RIM/ELKS C-terminal peptide complex using NMR spectroscopy. The structure shows that the RIM PDZ domain contains an unusually deep and narrow peptide-binding groove with an exquisite shape complementarity to the four ELKS C-terminal residues in their bound conformation. This groove is formed, in part, by a set of side-chains that is conserved selectively in RIM PDZ domains and that hence determines, at least in part, their unique specificity. (c) 2005 Elsevier Ltd. All rights reserved.