Distinct functional domains in emerin bind lamin A and DNA-bridging protein BAF.
Distinct functional domains in emerin bind lamin A and DNA-bridging protein BAF.
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发表时间：
2001-12
影响因子：
4
通讯作者：
Kenneth K. Lee;T. Haraguchi;R. S. Lee;T. Koujin;Y. Hiraoka;K. Wilson
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作者：
Kenneth K. Lee;T. Haraguchi;R. S. Lee;T. Koujin;Y. Hiraoka;K. Wilson
emerin（一种结合核膜蛋白的核膜蛋白）的缺失会导致emeri - dreifuss肌营养不良症。我们分析了13个位点定向突变和4个不破坏emerin稳定性或定位的致病突变。我们发现emerin直接与dna桥接蛋白BAF结合，并且这种与BAF的结合需要emerin的lem基序中的保守残基。Emerin有两个不同的功能结构域：位于n端的lem结构域，介导与BAF的结合，以及位于中心区域的第二个功能结构域，介导与层粘连蛋白a的结合。疾病突变Delta95-99映射到层粘连蛋白结合结构域，并在体外破坏层粘连蛋白a的结合。另外两个与疾病相关的残基Ser54和Pro183位于BAF和层粘连蛋白结合结构域之外，这表明emerin可能具有与疾病相关的其他功能结构域。无论在体内还是体外，与疾病相关的emerin蛋白都在与BAF结合时保持活性，这表明疾病可能是由于emerin与层粘连蛋白A或假定的新伴侣之间特异性分子相互作用的丧失而导致的。emerin直接与BAF结合的证明，加上LAP2的类似结果，原则上证明了所有lem结构域核蛋白都可以与BAF相互作用，这对染色质附着在核膜上具有有趣的意义。
Loss of emerin, a lamin-binding nuclear membrane protein, causes Emery-Dreifuss muscular dystrophy. We analyzed 13 site-directed mutations, and four disease-causing mutations that do not disrupt emerin stability or localization. We show that emerin binds directly to barrier-to-autointegration factor (BAF), a DNA-bridging protein, and that this binding to BAF requires conserved residues in the LEM-motif of emerin. Emerin has two distinct functional domains: the LEM-domain at the N-terminus, which mediates binding to BAF, and a second functional domain in the central region, which mediates binding to lamin A. Disease mutation Delta95-99 mapped to the lamin-binding domain and disrupted lamin A binding in vitro. Two other disease-linked residues, Ser54 and Pro183, mapped outside the BAF and lamin-binding domains, suggesting that emerin may have additional functional domains relevant to disease. The disease-linked emerin proteins all remained active for binding to BAF, both in vitro and in vivo, suggesting that disease can result from the loss of specific molecular interactions between emerin and either lamin A or putative novel partner(s). The demonstration that emerin binds directly to BAF, coupled to similar results for LAP2, provides proof in principle that all LEM-domain nuclear proteins can interact with BAF, with interesting implications for chromatin attachment to the nuclear envelope.