Max F. Perutz Laboratories, Medical University of Vienna, Dr. Bohr-Gasse 9, Vienna, Austria.
Biochem Soc Trans. 2011 Dec;39(6):1735-41. doi: 10.1042/BST20110724.
The nuclear envelope in eukaryotic cells has important roles in chromatin organization. The inner nuclear membrane contains over 60 transmembrane proteins. LEM [LAP2 (lamina-associated polypeptide 2)/emerin/MAN1] domain-containing proteins of the inner nuclear membrane are involved in tethering chromatin to the nuclear envelope and affect gene expression. They contain a common structural, bihelical motif, the so-called LEM domain, which mediates binding to a conserved chromatin protein, BAF (barrier to autointegration factor). Interestingly, this domain is highly related to other bihelical motifs, termed HeH (helix-extension-helix) and SAP {SAF (scaffold attachment factor)/acinus/PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)]} motifs, which are directly linked to DNA. In the present paper, we summarize evidence that the LEM motif evolved from the HeH and SAP domains concomitantly with BAF. In addition, we discuss the potential evolution of HeH/SAP and LEM domain-containing proteins and their role in chromatin tethering and gene regulation from unicellular eukaryotes to mammals.
真核细胞的核膜在染色质组织中具有重要作用。核内膜含有超过 60 种跨膜蛋白。核内膜中的 LEM [LAP2（核层相关多肽 2）/emerin/MAN1]结构域蛋白参与将染色质固定到核膜，并影响基因表达。它们含有一个常见的结构双螺旋基序，即所谓的 LEM 结构域，该结构域介导与保守的染色质蛋白 BAF（自动整合因子的屏障）的结合。有趣的是，该结构域与其他双螺旋基序高度相关，称为 HeH（螺旋-延伸-螺旋）和 SAP（支架附着因子/acinus/PIAS[STAT（信号转导和转录激活因子）激活的蛋白抑制剂]）基序，它们直接与 DNA 相连。在本文中，我们总结了证据，证明 LEM 基序是与 BAF 一起从 HeH 和 SAP 结构域进化而来的。此外，我们还讨论了从单细胞真核生物到哺乳动物的 HeH/SAP 和 LEM 结构域蛋白的潜在进化及其在染色质固定和基因调控中的作用。
