Crystal structure and cell surface anchorage sites of laminin α1LG4-5
Crystal structure and cell surface anchorage sites of laminin α1LG4-5
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DOI：
10.1074/jbc.m610657200
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发表时间：
2007-04-13
影响因子：
4.8
通讯作者：
Hohenester, Erhard
中科院分区：
文献类型：
--
作者：
Harrison, David;Hussain, Sadaf-Ahmahni;Hohenester, Erhard
层粘连蛋白-111是一种在胚胎发育过程中广泛表达的糖蛋白，其类层粘连蛋白结构域提供细胞锚定和受体结合部位，参与基底膜组装和细胞信号转导。我们现在报告层粘连蛋白α1LG4-5结构域的晶体结构，并提供肝素、α-营养不良聚糖和半乳糖硫脂结合的突变分析。α1LG4-5的两个结构域以类似于层粘连蛋白α2 LG4-5的V形方式排列，但具有本质上不同的结构域间角度。重组α1LG4-5与肝素、α-营养不良聚糖和硫脂的结合依赖于分布在LG4表面几个簇中的碱性残基的共同和独特贡献。对于肝素，最大的贡献来自两个簇，(RKR)-R-2719和(KRK)-K-2791。与α-营养不良聚糖的结合特别依赖于(RKR)-R-2719、(2831)RAR和(KDR)-K-2858中的碱性残基。受(2831)RAR和(2766)KGRTK突变影响最大的是(2831)RAR和(2766)KGRTK突变，而不是(RKR)-R-2719突变。结构和活性的联合分析揭示了LG结构域相互作用的差异，这应该能够剖析不同层粘连蛋白配体的生物学作用。
The laminin G-like ( LG) domains of laminin-111, a glycoprotein widely expressed during embryogenesis, provide cell anchoring and receptor binding sites that are involved in basement membrane assembly and cell signaling. We now report the crystal structure of the laminin alpha 1LG4-5 domains and provide a mutational analysis of heparin, alpha-dystroglycan, and galactosyl-sulfatide binding. The two domains of alpha 1LG4-5 are arranged in a V-shaped fashion similar to that observed with laminin alpha 2 LG4-5 but with a substantially different interdomain angle. Recombinant alpha 1LG4-5 binding to heparin, alpha-dystroglycan, and sulfatides was dependent upon both shared and unique contributions from basic residues distributed in several clusters on the surface of LG4. For heparin, the greatest contribution was detected from two clusters, (RKR)-R-2719 and (KRK)-K-2791. Binding to alpha-dystroglycan was particularly dependent on basic residues within (RKR)-R-2719, (2831)RAR, and (KDR)-K-2858. Binding to galactosyl-sulfatide was most affected by mutations in (2831)RAR and (2766)KGRTK but not in (RKR)-R-2719. The combined analysis of structure and activities reveal differences in LG domain interactions that should enable dissection of biological roles of different laminin ligands.