Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Proteins. 2010 Dec;78(16):3409-27. doi: 10.1002/prot.22848. Epub 2010 Oct 11.
Basement membranes are thin extracellular protein layers, which separate endothelial and epithelial cells from the underlying connecting tissue. The main noncollagenous components of basement membranes are laminins, trimeric glycoproteins, which form polymeric networks by interactions of their N-terminal (LN) domains; however, no high-resolution structure of laminin LN domains exists so far. To construct models for laminin β(1) and γ(1) LN domains, 14 potentially suited template structures were determined using fold recognition methods. For each target/template-combination comparative models were created with Rosetta. Final models were selected based on their agreement with experimentally obtained distance constraints from natural cross-links, that is, disulfide bonds as well as chemical cross-links obtained from reactions with two amine-reactive cross-linkers. We predict that laminin β(1) and γ(1) LN domains share the galactose-binding domain-like fold.
基膜是薄的细胞外蛋白质层，将内皮细胞和上皮细胞与下面的连接组织分开。基膜的主要非胶原成分是层粘连蛋白，是三聚体糖蛋白，通过其 N 端（LN）结构域的相互作用形成聚合网络；然而，到目前为止，还没有层粘连蛋白 LN 结构域的高分辨率结构。为了构建层粘连蛋白β（1）和γ（1）LN 结构域的模型，使用折叠识别方法确定了 14 个潜在合适的模板结构。对于每个目标/模板组合，使用 Rosetta 创建了比较模型。最终模型是根据它们与天然交联物（即二硫键）以及用两种胺反应性交联剂反应获得的化学交联物的实验获得的距离约束的一致性来选择的。我们预测层粘连蛋白β（1）和γ（1）LN 结构域共享半乳糖结合域样折叠。
