pH-dependent conformational change of gastric mucin leads to sol-gel transition
pH-dependent conformational change of gastric mucin leads to sol-gel transition
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DOI：
10.1016/s0006-3495(99)77288-7
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发表时间：
1999-03-01
影响因子：
3.4
通讯作者：
Afdhal, NH
中科院分区：
文献类型：
--
作者：
Cao, XX;Bansil, R;Afdhal, NH
我们提出了动态光散射（DLS）和疏水染料结合数据，以阐明胃黏液在低pH下形成凝胶的能力的分子机制，这对胃黏液的屏障功能至关重要。稀粘蛋白溶液的DLS测量结果并不表明分子间的关联，但随着pH值的降低，测量到的扩散系数稳步下降，表明粒径明显增加。结合观察到的去极化散射比随pH值的降低而升高，这些结果表明胃黏液蛋白经历了构象的变化，从pH值大于或等于4时的随机线圈到pH值< 4时的各向异性扩展构象。黏蛋白与疏水荧光蛋白的结合随着pH值的降低而增加，表明向延伸构象的变化伴随着疏水结合位点的暴露。在浓粘蛋白溶液中，由DLS测量得出的结构因子S（q, t）从pH 7时的拉伸指数衰减变为pH 2时的幂律衰减，这是溶胶-凝胶过渡的特征。我们提出，在低pH下，通过疏水相互作用，这种构象变化促进了粘蛋白大分子之间的交联，而当粘蛋白溶液足够浓缩时，这反过来又导致了溶胶-凝胶转变。
We present dynamic light scattering (DLS) and hydrophobic dye-binding data in an effort to elucidate a molecular mechanism for the ability of gastric mucin to form a gel at low pH, which is crucial to the barrier function of gastric mucus. DLS measurements of dilute mucin solutions were not indicative of intermolecular association, yet there was a steady fall in the measured diffusion coefficient with decreasing pH, suggesting an apparent increase in size. Taken together with the observed rise in depolarized scattering ratio with decreasing pH, these results suggest that gastric mucin undergoes a conformational change from a random coil at pH greater than or equal to 4 to an anisotropic, extended conformation at pH < 4. The increased binding of mucin to hydrophobic fluorescent with decreasing pH indicates that the change to an extended conformation is accompanied by exposure of hydrophobic binding sites. In concentrated mucin solutions, the structure factor S(q, t) derived from DLS measurements changed from a stretched exponential decay at pH 7 to a power-law decay at pH 2, which is characteristic of a sol-gel transition. We propose that the conformational change facilitates cross-links among mucin macromolecules through hydrophobic interactions at low pH, which in turn leads to a sol-gel transition when the mucin solution is sufficiently concentrated.