The importance of intramolecular ion pairing in intermediate filaments.
The importance of intramolecular ion pairing in intermediate filaments.
复制标题
中间丝中分子内离子配对的重要性。
DOI：
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发表时间：
1995
影响因子：
11.1
通讯作者：
E. Fuchs
中科院分区：
文献类型：
--
作者：
A. Letai;E. Fuchs
由10 nm中间丝组成的核和细胞骨架网络可能在多细胞真核生物中普遍存在。它们可能在维持细胞的机械完整性方面发挥作用。除了核层外，在没有辅因子或相关蛋白的情况下，如果蛋白质在体外可以形成IF。下面我们提供的数据表明，IF蛋白的大的α螺旋“棒”结构域是由大量(多达50个)由相反电荷的残基形成的螺旋内离子对稳定的，这些离子位于四个残基之间。这些离子对有时涉及盘绕线圈IF段中高达30%的残基，可能对单个α螺旋棒的稳定性做出高达10-25kcal/mol(1kcal=4.18kJ)的贡献。这种稳定性很可能在体内和体外的IF网络的化学和物理稳定性中发挥重要作用。对其他螺旋卷曲蛋白的研究表明，螺旋内离子配对的选择不仅仅是螺旋卷曲蛋白固有的特性。相反，螺旋内离子对的选择程度与卷曲卷曲蛋白质参与高度有序的多分子相互作用的程度之间存在相关性--例如，在IF和肌球蛋白粗纤维中。某些IF蛋白--如表皮角蛋白--中可能存在的离子对倾向表明，单体水平上的潜在结构稳定性可能在胞质IF中二聚体和更高有序结构的非凡稳定性中发挥重要作用。
Nuclear and cytoskeletal networks of 10-nm intermediate filaments (IFs) are probably ubiquitous in multicellular eukaryotes. They likely play a role in maintaining the mechanical integrity of a cell. With the exception of the nuclear lamins, IF proteins can form IFs in vitro in the absence of cofactors or associated proteins. Below we present data suggesting that the large alpha-helical "rod" domains of IF proteins are stabilized by large numbers (up to 50) of intra-helical ion pairs formed by residues of opposite charge situated four residues apart. These many ion pairs, sometimes involving up to 30% of the residues within a coiled-coil IF segment, can potentially contribute as much as 10-25 kcal/mol (1 kcal = 4.18 kJ) to the stability of a single alpha-helical rod. Such stabilization is likely to play a major role in the chemical and physical stability of IF networks in vitro and in vivo. An investigation of other coiled-coil proteins shows that selection for intrahelical ion pairing is not simply a property intrinsic to coiled-coil proteins. Rather, there is a correlation between the degree to which there is selection for intrahelical ion pairs and the extent to which a coiled-coil protein participates in highly ordered multimolecular interactions--e.g., as in IFs and myosin thick filaments. The propensity of putative ion pairs in some IF proteins--e.g., epidermal keratins--suggests that an underlying structural stability at the level of the monomer may play an important role in the extraordinary stability of dimers and higher ordered structures in cytoplasmic IFs.