The PDZ domain of the LIM protein enigma binds to β-tropomyosin
The PDZ domain of the LIM protein enigma binds to β-tropomyosin
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DOI：
10.1091/mbc.10.6.1973
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发表时间：
1999-06-01
影响因子：
3.3
通讯作者：
Gill, GN
中科院分区：
文献类型：
--
作者：
Guy, PM;Kenny, DA;Gill, GN
PDZ和LIM结构域是存在于具有不同功能的蛋白质中的模块化蛋白质相互作用基序。Enigma是由一系列保守的PDZ和LIM结构域组成的蛋白质家族的代表。Enigma的LIM结构域及其最相关的家族成员Enigma同源蛋白与蛋白激酶结合，而Enigma的PDZ结构域及其家族成员肌动蛋白相关的LIM蛋白与肌动蛋白丝结合。Enigma通过其PDZ结构域定位于成纤维细胞中的肌动蛋白丝，肌动蛋白相关的LIM蛋白在骨骼肌中的Z线处与肌动蛋白结合蛋白α-肌动蛋白-2结合并共定位。我们发现，谜是存在于骨骼肌中的Z线和谜的PDZ结构域结合到骨骼肌的目标，肌动蛋白结合蛋白原肌球蛋白（骨骼β-TM）。Enigma和骨骼beta-TM之间的相互作用对Enigma的PDZ结构域是特异性的，通过PDZ结构域中的突变而消除，并且需要骨骼beta-TM的最末端羧基端的PDZ结合共有序列（Thr-Ser-Leu）。Enigma与C2C12肌管中表达的原肌球蛋白亚型相互作用，并在转染细胞中与骨骼β-TM形成免疫沉淀复合物。Enigma与骨骼β-TM的关联表明Enigma作为一种衔接蛋白的作用，它将LIM结合蛋白引导到肌肉细胞的肌动蛋白丝上。
PDZ and LIM domains are modular protein interaction motifs present in proteins with diverse functions. Enigma is representative of a family of proteins composed of a series of conserved PDZ and LIM domains. The LIM domains of Enigma and its most related family member, Enigma homology protein, bind to protein kinases, whereas the PDZ domains of Enigma and family member actin-associated LIM protein bind to actin filaments. Enigma localizes to actin filaments in fibroblasts via its PDZ domain, and actin-associated LIM protein binds to and colocalizes with the actin-binding protein alpha-actinin-2 at Z lines in skeletal muscle. We show that Enigma is present at the Z line in skeletal muscle and that the PDZ domain of Enigma binds to a skeletal muscle target, the actin-binding protein tropomyosin (skeletal beta-TM). The interaction between Enigma and skeletal beta-TM was specific for the PDZ domain of Enigma, was abolished by mutations in the PDZ domain, and required the PDZ-binding consensus sequence (Thr-Ser-Leu) at the extreme carboxyl terminus of skeletal beta-TM. Enigma interacted with isoforms of tropomyosin expressed in C2C12 myotubes and formed an immunoprecipitable complex with skeletal beta-TM in transfected cells. The association of Enigma with skeletal beta-TM suggests a role for Enigma as an adapter protein that directs LIM-binding proteins to actin filaments of muscle cells.