McDermott L, Cooper A, Kennedy M W
Institute of Biomedical and Life Sciences and Department of Chemistry, University of Glasgow, Scotland, UK.
Mol Cell Biochem. 1999 Feb;192(1-2):69-75.
Parasitic nematodes have recently been found to produce proteins which represent two new classes of fatty acid and retinoid binding protein. The first is the nematode polyprotein allergens/antigens (NPAs) which, as their name suggests, are synthesised as large polyproteins which are subsequently cleaved at regularly spaced sites to form multiple copies of a fatty acid binding protein of approximately 14.5 kDa. Binding studies using molecular environment-sensitive fluorescent ligands have shown that the binding site is highly unusual, producing blue-shifting in fluorescence to an unprecedented degree, suggesting a remarkably non-polar environment and isolation from solvent water. Computer-based structural predictions and biophysical observations have identified the NPAs as highly helical proteins which might form a four helix bundle, so constitute a new class of lipid binding protein from animals. The second class, like the NPAs, binds both fatty acids and retinol, but with a higher affinity for the latter. These are also highly helical but are structurally distinct from the NPAs. The biological function of these new classes of protein are discussed in the context of both the metabolic requirements of the parasites and the possible role of the proteins in control of the immune and inflammatory environment of the tissue sites parasitised.
最近发现寄生线虫能产生代表两类新型脂肪酸和视黄醇结合蛋白的蛋白质。第一类是线虫多蛋白过敏原/抗原(NPA),顾名思义,它们最初是作为大的多蛋白合成的,随后在规则间隔的位点被切割,形成多个约14.5 kDa的脂肪酸结合蛋白拷贝。使用对分子环境敏感的荧光配体进行的结合研究表明,其结合位点非常独特,能使荧光发生前所未有的蓝移,这表明存在一个非常非极性的环境且与溶剂水隔离。基于计算机的结构预测和生物物理观察已确定NPA是高度螺旋的蛋白质,可能形成四螺旋束,因此构成了一类新的动物脂质结合蛋白。第二类蛋白与NPA一样,既能结合脂肪酸又能结合视黄醇,但对后者的亲和力更高。这些蛋白也是高度螺旋的,但在结构上与NPA不同。本文在寄生虫的代谢需求以及这些蛋白质在控制被寄生组织部位的免疫和炎症环境中可能发挥的作用的背景下,讨论了这些新型蛋白质的生物学功能。