The molecular basis of emerin-emerin and emerin-BAF interactions
The molecular basis of emerin-emerin and emerin-BAF interactions
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DOI：
10.1242/jcs.148247
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发表时间：
2014-09-15
影响因子：
4
通讯作者：
Wilson, Katherine L.
中科院分区：
文献类型：
--
作者：
Berk, Jason M.;Simon, Dan N.;Wilson, Katherine L.
Emerin是核纤层结构的保守膜组分。在这里，我们报告的进展，了解emerin功能的分子基础：分子间emerin-emerin协会。有两种模式：一种是由一个Emerin分子中的残基170-220与另一个Emerin分子中的残基170 - 220的结合介导的，第二种涉及残基170-220和1-132。缺失分析表明，残基187-220含有细胞中分子间缔合所必需的正元件。相比之下，残基168-186的缺失使限制或控制缔合所需的拟议负元件失活。在细胞中GFP-浮现蛋白与核BAF的关联需要LEM结构域（残基1-47）和阳性元件。Emerin肽阵列显示残基170-220与残基206-225（提出的阳性元件）、残基147-174（特别是P（153）MYGRDSAYQSITHYRP（169））和LEM结构域直接结合。Emerin残基1-132和159-220各自足以在体外结合核纤层蛋白A或B1尾部，鉴定了与核纤层蛋白分子接触的两个独立区域。这些结果，并预测emerin内在的障碍，支持的假设，有多个“骨干”和LEM结构域的配置在一个拟议的分子间emerin网络在核膜。
Emerin is a conserved membrane component of nuclear lamina structure. Here, we report an advance in understanding the molecular basis of emerin function: intermolecular emerin-emerin association. There were two modes: one mediated by association of residues 170-220 in one emerin molecule to residues 170-220 in another, and the second involving residues 170-220 and 1-132. Deletion analysis showed residues 187-220 contain a positive element essential for intermolecular association in cells. By contrast, deletion of residues 168-186 inactivated a proposed negative element, required to limit or control association. Association of GFP-emerin with nuclear BAF in cells required the LEM domain (residues 1-47) and the positive element. Emerin peptide arrays revealed direct binding of residues 170-220 to residues 206-225 (the proposed positive element), residues 147-174 (particularly P(153)MYGRDSAYQSITHYRP(169)) and the LEM domain. Emerin residues 1-132 and 159-220 were each sufficient to bind lamin A or B1 tails in vitro, identifying two independent regions of molecular contact with lamins. These results, and predicted emerin intrinsic disorder, support the hypothesis that there are multiple 'backbone' and LEM-domain configurations in a proposed intermolecular emerin network at the nuclear envelope.