The limits of promiscuity:: Isoform-specific dimerization of filamins
The limits of promiscuity:: Isoform-specific dimerization of filamins
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DOI：
10.1021/bi026501
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发表时间：
2003-01-21
期刊：
影响因子：
2.9
通讯作者：
Fürst, DO
中科院分区：
文献类型：
--
作者：
Himmel, M;van der Ven, PFM;Fürst, DO
丝状蛋白是肌动蛋白交联蛋白家族，主要定位于所有哺乳动物细胞的皮质细胞质中。到目前为止，已经鉴定了三种主要的同种型（丝状体a、B和c），其显示在不同组织中差异表达和/或定位。氨基末端的双CH-结构域肌动蛋白结合结构域和蛋白质羧基末端部分的二聚化区域是其肌动蛋白交联活性的分子基础。细菌表达的重组蛋白的化学交联用于证明在所有三种细丝蛋白亚型中，最羧基末端定位的免疫球蛋白样结构域是二聚化所需的并且是足够的。二聚化的效率增加后，包括前面的铰链2区，表明该区域在调节二聚化的功能。通过混合来自不同细丝蛋白亚型的重组蛋白，我们发现细丝蛋白B和C之间可能形成异二聚体，但细丝蛋白A和其他两种细丝蛋白之间不可能形成异二聚体。这种选择性的二聚体可能提供了一个进一步的分子解释的差异细胞内的细丝蛋白亚型和它们的独特性质的排序。
Filamins are a family of actin cross-linking proteins that are primarily localized in the cortical cytoplasm of all mammalian cells. Until now, three major isoforms (filamins a, b, and c) have been identified, that were shown to be differentially expressed and/or localized in different tissues. An amino-terminal double CH-domain actin binding domain, and a dimerization region in the carboxy-terminal portion of the protein are the molecular basis for its actin cross-linking, activity. Chemical cross-linking of bacterially expressed recombinant proteins was used to demonstrate that in all three filamin isoforms the most carboxy-terminally situated immunoglobulinlike domain is required and sufficient for dimerization. The efficiency of the dimerization was increased upon inclusion of the preceding hinge 2 region, indicating a function for this region in the regulation of dimerization. By mixing recombinant proteins derived from different filamin isoforms, we found that heterodimer formation is possible between filamins b and c but not between filamin a and the other two filamins. This selectivity of dimerization might provide a further molecular explanation for the differential intracellular sorting of filamin isoforms and their distinct properties.