Solution structure of a type 2 module from fibronectin: Implications for the structure and function of the gelatin-binding domain
Solution structure of a type 2 module from fibronectin: Implications for the structure and function of the gelatin-binding domain
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DOI：
10.1016/s0969-2126(97)00193-7
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发表时间：
1997-03-15
期刊：
影响因子：
5.7
通讯作者：
Campbell, D
中科院分区：
文献类型：
--
作者：
Pickford, AR;Potts, JR;Campbell, D
背景：纤连蛋白是一种细胞外基质糖蛋白，参与一系列重要生理过程中的细胞粘附和迁移事件，细胞与基质的异常粘附可能导致与各种疾病相关的正常组织功能的破坏。纤连蛋白的粘附特性可能是通过其与胶原蛋白（最丰富的细胞外基质蛋白）的相互作用介导的。纤连蛋白的胶原蛋白结合活性已定位于 42 kDa 蛋白水解片段，基于该片段对变性胶原蛋白（明胶）的亲和力。该明胶结合结构域包含蛋白质中唯一的 2 型 (F2) 模块。基质金属蛋白酶 MMP2 和 MMP9 的 F2 模块负责这些蛋白质与明胶的亲和力。了解纤连蛋白的结构将有助于深入了解其与其他蛋白质的相互作用，并将有助于我们了解正常组织和疾病改变组织中细胞外基质的结构和功能。结果：我们通过二维核磁共振波谱确定了人纤连蛋白第一个 F2 ((1)F2) 模块的溶液结构。(1)F2 模块的三级结构类似于较短的 F2 模块 PDC-109b，来自牛精浆蛋白 PDC-109，(1)F2 模块具有两个彼此大致垂直的双链反平行 β 片层，并包围一簇高度保守的芳香残基，其中五个形成溶剂暴露的疏水表面。(1)F2 中的 N 端延伸使模块的 N 和 C 末端非常接近。结论：(1)F2 中 N 和 C 末端的紧密接近允许之间的相互作用因此，该结构域可能具有更紧凑的球状结构，而不是形成延伸的线性模块链。模块暴露于溶剂的疏水表面中的口袋可以结合细胞外基质成分 I 型胶原的假定纤连蛋白结合位点中的非极性残基。
Background: Fibronectin is an extracellular matrix glycoprotein involved in cell adhesion and migration events in a range of important physiological processes, Aberrant adhesion of cells to the matrix may contribute to the breakdown of normal tissue function associated with various diseases. The adhesive properties of fibronectin may be mediated by its interaction with collagen, the most abundant extracellular matrix protein. The collagen-binding activity of fibronectin has been localized to a 42 kDa proteolytic fragment on the basis of this fragment's affinity for denatured collagen (gelatin). This gelatin-binding domain contains the only type 2 (F2) modules found in the protein. The F2 modules of the matrix metalloproteinases MMP2 and MMP9 are responsible for the affinity of these proteins for gelatin. Knowledge of the structure of fibronectin will provide insights into its interactions with other proteins, and will contribute to our understanding of the structure and function of the extracellular matrix, in both normal and disease-altered tissues.Results: We have determined the solution structure of the first F2 ((1)F2) module from human fibronectin by two-dimensional NMR spectroscopy, The tertiary structure of the (1)F2 module is similar to that of a shorter F2 module, PDC-109b, from the bovine seminal plasma protein PDC-109, The (1)F2 module has two double-stranded antiparallel beta sheets oriented approximately perpendicular to each other, and enclosing a cluster of highly conserved aromatic residues, five of which form a solvent-exposed hydrophobic surface, The N-terminal extension in(1)F2 brings the N and C termini of the module into close proximity.Conclusions: The close proximity of the N and C termini in (1)F2 allows for interactions between non-contiguous modules in the gelatin-binding domain, Thus, instead of forming an extended, linear chain of modules, the domain may have a more compact, globular structure, A pocket in the module's solvent-exposed hydrophobic surface may bind nonpolar residues in the putative fibronectin-binding site of the extracellular matrix component type I collagen.