Bocquier A A, Potts J R, Pickford A R, Campbell I D
Department of Biochemistry, University of Oxford, UK.
Structure. 1999 Dec 15;7(12):1451-60. doi: 10.1016/s0969-2126(00)88336-7.
Fibronectin has a role in vital physiological processes such as cell migration during embryogenesis and wound healing. It mediates the attachment of cells to extracellular matrices that contain fibrous collagens. The affinity of fibronectin for native collagen and denatured collagen (gelatin) is located within a 42 kDa domain that contains four type 1 (F1) and two type 2 (F2) modules. A putative ligand-binding site has been located on an isolated F2 module, but the accessibility of this site in the intact domain is unknown. Thus, structural studies of module pairs and larger fragments are required for a better understanding of the interaction between fibronectin and collagen.
The solution structure of the 101-residue 6F1 1F2 module pair, which has a weak affinity for gelatin, has been determined by multidimensional NMR spectroscopy. The tertiary structures determined for each module conform to the F1 and F2 consensus folds established previously. The experimental data suggest that the two modules interact via a small hydrophobic interface but may not be tightly associated. Near-random-coil 1H NMR chemical shifts and fast dynamics for backbone atoms in the linker indicate that this region is unlikely to be involved in the overall stabilisation of the module pair.
The modules in the 6F1 1F2 module pair interact with each other via a flexible linker and a hydrophobic patch, which lies on the opposite side of the 1F2 module to the putative collagen-binding site. The intermodule interaction is relatively weak and transient.
纤连蛋白在重要的生理过程中发挥作用，如胚胎发育和伤口愈合过程中的细胞迁移。它介导细胞与含有纤维状胶原蛋白的细胞外基质的附着。纤连蛋白对天然胶原蛋白和变性胶原蛋白（明胶）的亲和力位于一个42 kDa的结构域内，该结构域包含四个1型（F1）和两个2型（F2）模块。一个假定的配体结合位点已定位在一个分离的F2模块上，但该位点在完整结构域中的可及性尚不清楚。因此，需要对模块对和更大片段进行结构研究，以更好地理解纤连蛋白与胶原蛋白之间的相互作用。
通过多维核磁共振光谱法确定了对明胶亲和力较弱的101个残基的6F1 1F2模块对的溶液结构。为每个模块确定的三级结构符合先前建立的F1和F2共有折叠。实验数据表明，这两个模块通过一个小的疏水界面相互作用，但可能结合不紧密。连接子中主链原子的近随机卷曲1H NMR化学位移和快速动力学表明，该区域不太可能参与模块对的整体稳定。
6F1 1F2模块对中的模块通过一个柔性连接子和一个疏水斑块相互作用，该疏水斑块位于1F2模块与假定的胶原蛋白结合位点相对的一侧。模块间的相互作用相对较弱且短暂。
