Crystal structure of the LG1-3 region of the laminin alpha2 chain.
Crystal structure of the LG1-3 region of the laminin alpha2 chain.
复制标题
DOI：
10.1074/jbc.m109.026658
复制
发表时间：
2009-08-21
期刊：
影响因子：
--
通讯作者：
Hohenester E
中科院分区：
文献类型：
--
作者：
Carafoli F;Clout NJ;Hohenester E
层粘连蛋白是在基底膜组装和功能中具有许多基本功能的大的异源三聚体糖蛋白。细胞与层粘连蛋白的粘附由α链C端的五个层粘连蛋白G样（LG）结构域串联介导。整合素结合需要完整的LG 1 -3区域，以及来自α、β和γ链形成的卷曲螺旋的贡献。我们测定了层粘连蛋白α2链（α 2LG 1 -3）的LG 1 -3区的晶体结构，其分辨率为2.8 μ m。三个LG结构域采用典型的β-夹心折叠，在LG 1和LG 2中具有典型的钙结合位点。LG 2和LG 3通过实质性界面相互作用，但LG 1完全从LG 2 -3对中解离。我们认为，丢失的γ链尾可能是稳定LG 1和LG 2 -3之间的相互作用所必需的。N-连接糖基化位点的全局分析显示，LG 1的β-夹心面在所有五条层粘连蛋白α链中均不含碳水化合物修饰，表明这些表面可能含有整合素结合位点。α 2LG 1 -3结构提供了层粘连蛋白的整合素结合区域的第一个原子视图。
Laminins are large heterotrimeric glycoproteins with many essential functions in basement membrane assembly and function. Cell adhesion to laminins is mediated by a tandem of five laminin G-like (LG) domains at the C terminus of the α chain. Integrin binding requires an intact LG1-3 region, as well as contributions from the coiled coil formed by the α, β, and γ chains. We have determined the crystal structure at 2.8-Å resolution of the LG1-3 region of the laminin α2 chain (α2LG1-3). The three LG domains adopt typical β-sandwich folds, with canonical calcium binding sites in LG1 and LG2. LG2 and LG3 interact through a substantial interface, but LG1 is completely dissociated from the LG2-3 pair. We suggest that the missing γ chain tail may be required to stabilize the interaction between LG1 and LG2-3 in the biologically active conformation. A global analysis of N-linked glycosylation sites shows that the β-sandwich faces of LG1 are free of carbohydrate modifications in all five laminin α chains, suggesting that these surfaces may harbor the integrin binding site. The α2LG1-3 structure provides the first atomic view of the integrin binding region of laminins.