Tang Huadong, Fu Yan, Cui Yujie, He Yingbo, Zeng Xing, Ploplis Victoria A, Castellino Francis J, Luo Yongzhang
National Engineering Laboratory for Anti-tumor Protein Therapeutics Tsinghua University, Beijing 100084, China.
Biochem Biophys Res Commun. 2009 Jan 16;378(3):662-7. doi: 10.1016/j.bbrc.2008.11.112. Epub 2008 Dec 4.
Partially or completely unfolded polypeptides are highly prone to aggregation due to nonspecific interactions between their exposed hydrophobic surfaces. Extracellular proteins are continuously subjected to stresses conditions, but the existence of extracellular chaperones remains largely unexplored. The results presented here demonstrate that one of the most abundant extracellular proteins, fibrinogen has chaperone-like activity. Fibrinogen can specifically bind to nonnative form of citrate synthase and inhibit its thermal aggregation and inactivation in an ATP-independent manner. Interestingly, fibrinogen maintains thermal-denatured luciferase in a refolding competent state allowing luciferase to be refolded in cooperation with rabbit reticulocyte lysate. Fibrinogen also inhibits fibril formation of yeast prion protein Sup35 (NM). Furthermore, fibrinogen rescues thermal-induced protein aggregation in the plasma of fibrinogen-deficient mice. Our studies demonstrate the chaperone-like activity of fibrinogen, which not only provides new insights into the extracellular chaperone protein system, but also suggests potential diagnostic and therapeutic approaches to fibrinogen-related pathological conditions.
部分或完全展开的多肽由于其暴露的疏水表面之间的非特异性相互作用而极易聚集。细胞外蛋白质不断受到应激条件的影响，但细胞外伴侣蛋白的存在在很大程度上仍未被探索。此处呈现的结果表明，最丰富的细胞外蛋白质之一纤维蛋白原具有伴侣样活性。纤维蛋白原可以特异性结合柠檬酸合酶的非天然形式，并以不依赖ATP的方式抑制其热聚集和失活。有趣的是，纤维蛋白原将热变性的荧光素酶维持在可重折叠状态，使荧光素酶能够与兔网织红细胞裂解物协同重折叠。纤维蛋白原还抑制酵母朊病毒蛋白Sup35（NM）的原纤维形成。此外，纤维蛋白原可挽救纤维蛋白原缺陷小鼠血浆中的热诱导蛋白聚集。我们的研究证明了纤维蛋白原的伴侣样活性，这不仅为细胞外伴侣蛋白系统提供了新的见解，也为纤维蛋白原相关病理状况提示了潜在的诊断和治疗方法。
