Molten-Globule of Proteins and Its Physiological Role

熔融球是一种致密的变性状态，具有大量的二级结构，但很大程度上是无序的三级结构。为了了解熔融球在蛋白质折叠中的作用及其生理作用，我们研究了各种蛋白质的熔融球的构象和稳定性以及肽的相应状态。取得了以下主要成果：1.熔融球的稳定性取决于各种力的平衡。我们发现静电斥力是使熔融球态不稳定的关键因素.利用小角X射线散射技术研究了细胞色素c熔融球的构象特征.研究表明，在生理条件下（即中性ph、生理温度和无变性剂），细胞色素c的可逆变性构象为熔融球.揭示了蜂毒肽和两亲性多肽构象转变的阴离子和ph依赖性机理.我们发现盐酸胍诱导酸解折叠蛋白质的重折叠，稳定熔融球状态。

The molten globule is a compact denatured state with a significant amount of secondary structure, but largely disordered tertiary structure. To understand the role of the molten globule in protein folding and its physiological role, we studied the conformation and stability of the molten globule of various proteins and the corresponding state of peptides. We obtained following major results.1. The stability of the molten globule is determined by a balance of various forces. We showed that electrostatic repulsion is a critical factor destabilizing the molten globule state.2. The molten globule of cytochrome c was studied by small angle X-ray scattering and its conformational properties were clarified.3. We indicated that the reversibly denatured conformation of cytochrome c under physiological conditions (i.e. neutral ph, physiological temperature and no denaturant) is the molten globule.4. We showed the mechanism of the anion and ph-dependent conformational transition of melittin and an amphiphilic polypeptide.5. We showed that Guanidine-Hydrochloride induces the refolding of acid-unfolded proteins, stabilizing the molten globule state.