Lequin Olivier, Staunton David, Mulloy Barbara, Forster Mark J, Yoshida Keiichi, Campbell Iain D
Department of Biochemistry and Oxford Centre for Molecular Sciences, University of Oxford, South Parks Rd., Oxford OX1 3QU, United Kingdom.
J Biol Chem. 2002 Dec 27;277(52):50629-35. doi: 10.1074/jbc.M208956200. Epub 2002 Oct 10.
Fibronectin, a multifunctional glycoprotein of the extracellular matrix, plays a major role in cell adhesion. Various studies have revealed that the human 13th and 14th fibronectin type III domains (labeled (13)F3 and (14)F3 here) contain a heparin-binding site. Mapping of the heparin-binding sites of (13-14)F3, (13)F3, and (14)F3 by NMR chemical shift perturbation, isothermal titration calorimetry, and molecular modeling show that (13)F3 provides the dominant heparin-binding site and that the residues involved are within the first 29 amino acids of (13)F3. Predictions from earlier biochemical and modeling studies as well as the x-ray structure of (12-14)F3 were tested. It was shown that the positively charged residues that project into the solvent from the ABE face of the triple-stranded beta sheet on (13)F3 are involved in binding, but (14)F3 does not appear to contribute significantly to heparin binding.
纤连蛋白是细胞外基质中的一种多功能糖蛋白，在细胞黏附中起主要作用。各种研究表明，人第13和14个III型纤连蛋白结构域（此处标记为(13)F3和(14)F3）含有一个肝素结合位点。通过核磁共振化学位移扰动、等温滴定量热法和分子模拟对(13 - 14)F3、(13)F3和(14)F3的肝素结合位点进行定位，结果表明(13)F3提供了主要的肝素结合位点，且相关残基位于(13)F3的前29个氨基酸内。对早期生化和模型研究以及(12 - 14)F3的x射线结构所做的预测进行了验证。结果表明，从(13)F3上三链β折叠的ABE面伸向溶剂的带正电荷残基参与了结合，但(14)F3似乎对肝素结合没有显著贡献。
