Structural analysis of collagen type I interactions with human fibronectin reveals a cooperative binding mode.
Structural analysis of collagen type I interactions with human fibronectin reveals a cooperative binding mode.
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I型I型与人纤连蛋白的胶原蛋白相互作用的结构分析揭示了一种合作结合模式。
DOI：
10.1074/jbc.m113.469841
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发表时间：
2013-06-14
期刊：
影响因子：
--
通讯作者：
Vakonakis I
中科院分区：
文献类型：
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作者：
Erat MC;Sladek B;Campbell ID;Vakonakis I
背景：纤维连接蛋白（FN）与胶原蛋白的相互作用对细胞粘附和迁移至关重要。结果：FN模块8-9FnI与胶原i链中两个不同的位点相互作用。所有六个胶原结合FN模块与单个胶原位点相互作用。结论：I型胶原蛋白具有4个FN等位位点。意义：我们绘制了FN与I型胶原结合的图谱，并展示了第一次合作相互作用。尽管具有重要的生物学意义，但纤维连接蛋白（FN）和胶原蛋白这两种丰富而重要的组织成分之间的相互作用尚未在结构水平上得到很好的表征。在这里，我们使用溶液核磁共振、荧光和小角度x射线散射方法分析了I型胶原表位与人类FN的胶原结合片段（明胶结合域（GBD））之间形成的四种相互作用。胶原蛋白与FN模块8-9FnI的关联是通过保守的结构机制发生的，但在胶原位点之间表现出400倍的亲和力差异。在全长GBD中，由于6FnI1-2FnII7FnI在最弱的8 - 9fni结合位点附近结合了一个特定的胶原表位，这种差异减小了。所有GBD模块与胶原蛋白的协同作用产生了四个大致相同的fn -胶原相互作用位点。胶原结合稳定了溶液中独特的单体GBD构象，进一步证明了FN片段形成明确的功能和结构单位的观点。
Background: The fibronectin (FN)-collagen interaction is important for cell adhesion and migration. Results: FN modules 8–9FnI interact with two distinct sites in both chains of collagen I. All six collagen-binding FN modules interact cooperatively with a single collagen site. Conclusion: Collagen I possesses four equipotent sites for FN. Significance: We have mapped FN binding to collagen I and demonstrated the first cooperative interaction. Despite its biological importance, the interaction between fibronectin (FN) and collagen, two abundant and crucial tissue components, has not been well characterized on a structural level. Here, we analyzed the four interactions formed between epitopes of collagen type I and the collagen-binding fragment (gelatin-binding domain (GBD)) of human FN using solution NMR, fluorescence, and small angle x-ray scattering methods. Collagen association with FN modules 8–9FnI occurs through a conserved structural mechanism but exhibits a 400-fold disparity in affinity between collagen sites. This disparity is reduced in the full-length GBD, as 6FnI1–2FnII7FnI binds a specific collagen epitope next to the weakest 8–9FnI-binding site. The cooperative engagement of all GBD modules with collagen results in four broadly equipotent FN-collagen interaction sites. Collagen association stabilizes a distinct monomeric GBD conformation in solution, giving further evidence to the view that FN fragments form well defined functional and structural units.