School of Sciences, Information Technology and Engineering, University of Ballarat, Mount Helen, Ballarat, Victoria 3353, Australia.
J Biomol Struct Dyn. 2011 Jun;28(6):861-9. doi: 10.1080/07391102.2011.10508613.
Prion diseases such as Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob diseases, Gerstmann-Sträussler-Scheinker syndrome, Fatal Familial Insomnia, Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (or 'mad-cow' disease) and chronic wasting disease in cattle are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. However, by now there have not been some effective therapeutic approaches to treat all these prion diseases. In 2008, canine mammals including dogs (canis familials) were the first time academically reported to be resistant to prion diseases (Vaccine 26: 2601-2614 (2008)). Thus, it is very worth studying the molecular structures of dog prion protein to obtain insights into the immunity of dogs to prion diseases. This paper studies the molecular structural dynamics of wild-type dog prion protein. The comparison analyses with rabbit prion protein show that the dog prion protein has stable molecular structures whether under neutral or low pH environments. We also find that the salt bridges such as D177-R163 contribute to the structural stability of wild-type rabbit prion protein under neutral pH environment.
朊病毒疾病,如克雅氏病、变异型克雅氏病、格斯特曼-斯召斯列综合征、致命性家族性失眠症、人类库鲁病、羊瘙痒病、牛海绵状脑病(或“疯牛病”)和牛慢性消瘦病,都是不可避免致命和高度传染性的神经退行性疾病,影响人类和动物。然而,到目前为止,还没有一些有效的治疗方法来治疗所有这些朊病毒疾病。2008 年,犬科哺乳动物(包括狗)首次被学术报道对朊病毒疾病具有抗性(Vaccine 26: 2601-2614 (2008))。因此,研究犬朊病毒蛋白的分子结构以了解犬对朊病毒疾病的免疫反应非常值得。本文研究了野生型犬朊病毒蛋白的分子结构动力学。与兔朊病毒蛋白的比较分析表明,犬朊病毒蛋白在中性或低 pH 环境下具有稳定的分子结构。我们还发现,D177-R163 等盐桥有助于中性 pH 环境下野生型兔朊病毒蛋白的结构稳定性。