Beta-strand-mediated dimeric formation of the Ig-like domains of human lamin A/C and B1
Beta-strand-mediated dimeric formation of the Ig-like domains of human lamin A/C and B1
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DOI：
10.1016/j.bbrc.2021.02.102
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发表时间：
2021-03-09
影响因子：
3.1
通讯作者：
Ha, Nam-Chul
中科院分区：
文献类型：
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作者：
Ahn, Jinsook;Lee, Jinwook;Ha, Nam-Chul
核纤层蛋白是核中间丝蛋白，通过形成 3-D 网络在维持核结构中发挥重要作用。核纤层蛋白由 N 端非结构化头部、卷曲线圈杆结构域和 C 端尾部组成，除了 Ig 样结构域外，C 端尾部大部分是非结构化的。迄今为止，Ig 样结构域已被表征为单体结构。在这里，我们确定了人核纤层蛋白 A/C 的晶体结构，包括 Ig 样结构域及其 N 端和 C 端侧翼序列。有趣的是，这些结构显示出由 N 端和 C 端侧翼序列之间的 β 链相互作用形成的同二聚体。这种相互作用还为在 3.5 nm 厚的细丝之间创建 3-D 网格提供了分子意义。此外，我们还确定了核纤层蛋白B1相应区域的晶体结构。该结构显示出类似的二聚体组装，也是由β链相互作用形成的，尽管亚基间距离要短得多。由于 Ig 样结构域包含许多导致核纤层蛋白 A/C 中核纤层蛋白相关疾病的遗传热点，我们的研究结果将有助于在分子水平上了解 3-D 网状结构中核纤层蛋白的详细组装以及核纤层蛋白相关疾病。(c) 2021 年由 Elsevier Inc. 出版。
Lamins are nuclear intermediate filament proteins that play an essential role in maintaining the nuclear structure by forming a 3-D meshwork. Lamins consist of the N-terminal unstructured head, the coiled coil rod domain, and the C-terminal tail, which is mostly unstructured except for the Ig-like domain. To date, the Ig-like domain has been characterized as a monomeric structure. Here, we determined the crystal structures of human lamin A/C, including the Ig-like domain and its N-and C-terminal flanking sequences. Interestingly, the structures showed a homodimer formed by beta-strand interactions between the N-and C-terminal flanking sequences. This interaction also provides a molecular implication for the creation of a 3-D meshwork between the 3.5-nm-thick filaments. Furthermore, we determined the crystal structure of the corresponding region of lamin B1. The structure showed a similar dimeric assembly, also formed by beta-strand interactions, albeit the intersubunit distance was much shorter. Since the Ig-like domain contains many genetic hotspots causing lamin-related diseases in lamin A/C, our findings will help understand the detailed assembly of lamins in a 3-D meshwork structure and laminrelated diseases at the molecular level.(c) 2021 Published by Elsevier Inc.