Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA
Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA
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DOI：
10.1093/emboj/20.16.4399
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发表时间：
2001-08-15
期刊：
影响因子：
11.4
通讯作者：
Clore, GM
中科院分区：
文献类型：
--
作者：
Cai, ML;Huang, Y;Clore, GM
核膜蛋白LAP2、Emerin和MAN1具有类似于40个残基的保守‘LEM’基序。Emerin的丢失会导致Emery-Dreifuss肌营养不良症。我们已经解决了人LAP2(残基1-168)恒定区的溶液核磁共振结构。人LAP2(1-168)有两个结构独立、不相互作用的结构域，分别位于残基1-50(‘LAP2-N’)和残基111-152(LEM-结构域)，由类似于60个残基的柔性连接子连接。这两个结构域在结构上是同源的，包括一个螺旋旋转，随后是两个由11-12残基环连接的螺旋。这个基序由T4内切酶VII和转录因子Rho的亚域共享，尽管序列同源性可以忽略不计(小于或等于15%)。核磁共振化学位移图谱显示LEM结构域与BAF(屏障自整合因子)结合，而LAP2-N与DNA结合。两个结合表面都包括螺旋1、螺旋2的N末端和螺旋间环。结合选择性由这些结合部位的表面残基的性质决定，这些结合部位的表面残基对LAP2-N主要是正电荷，对LEM-结构域是疏水的。因此，LEM和LEM类基序形成了一个共同的结构，进化为与BAF或DNA结合而定制。
The nuclear envelope proteins LAP2, emerin and MAN1 share a conserved similar to 40-residue 'LEM' motif. Loss of emerin causes Emery-Dreifuss muscular dystrophy. We have solved the solution NMR structure of the constant region of human LAP2 (residues 1-168). Human LAP2(1-168) has two structurally independent, non-interacting domains located at residues 1-50 ('LAP2-N') and residues 111-152 (LEM-domain), connected by an similar to 60-residue flexible linker. The two domains are structurally homologous, comprising a helical turn followed by two helices connected by an 11-12-residue loop. This motif is shared by subdomains of T4 endonuclease VII and transcription factor rho, despite negligible (less than or equal to 15%) sequence identity. NMR chemical shift mapping demonstrated that the LEM-domain binds BAF (barrier-to-autointegration factor), whereas LAP2-N binds DNA. Both binding surfaces comprise helix 1, the N-terminus of helix 2 and the inter-helical loop. Binding selectivity is determined by the nature of the surface residues in these binding sites, which are predominantly positively charged for LAP2-N and hydrophobic for the LEM-domain. Thus, LEM and LEM-like motifs form a common structure that evolution has customized for binding to BAF or DNA.