Boutin Jean A, Li Zhuolun, Vuillard Laurent, Vénien-Bryan Catherine
Pôle d'expertise Biotechnologie, Chimie et Biologie, Institut de Recherches Servier, 125, chemin de Ronde, 78290 Croissy-sur-Seine, France.
Institut de minéralogie, de physique des matériaux et de cosmochimie, UMR 7590, CNRS, UPMC, IRD, MNHN, 75005 Paris, France.
Med Sci (Paris). 2016;32(8-9):758-67. doi: 10.1051/medsci/20163208025. Epub 2016 Sep 12.
Recent technological advances have revolutionized the field of structural biologists. Specifically, dramatic progress related to the development of new electron microscopes and image capture (direct electron detection camera) and the provision of new image analysis software has led to a breakthrough in terms of resolution attained using cryo-electron transmission microscopy. It is thus possible to calculate relatively quickly high-resolution structures of biological molecules whom structural study still resists to more conventional methods such as X-ray diffraction or nuclear magnetic resonance (NMR). These structures thus obtained may also bring complementary structural information to those already described by other methods. Some of these new structures resolved through cryo-electron microscopy revealed for the first time the precise operation of essential mechanisms necessary for the good physiological process of a cell. The ability to solve these structures at atomic resolution detail is essential for the development of new drugs that target these proteins of therapeutic interest. Thanks to these advanced techniques that we summarize in this revew, biological and medical issues have now become accessible, whereas this approach was inconceivable only five yeras ago. ‡.
最近的技术进步彻底改变了结构生物学家的领域。具体而言,新型电子显微镜及图像捕捉(直接电子检测相机)的发展以及新图像分析软件的提供取得了显著进展,这使得冷冻电子透射显微镜在分辨率方面取得了突破。因此,对于那些用诸如X射线衍射或核磁共振(NMR)等更传统方法仍难以进行结构研究的生物分子,可以相对快速地计算出其高分辨率结构。这样获得的这些结构也可能为其他方法已经描述的结构信息带来补充。通过冷冻电子显微镜解析的一些新结构首次揭示了细胞良好生理过程所必需的基本机制的精确运作。以原子分辨率细节解析这些结构的能力对于开发针对这些具有治疗意义的蛋白质的新药至关重要。多亏了我们在本综述中总结的这些先进技术,生物学和医学问题现在已经可以解决,而这种方法在仅仅五年前还是不可想象的。‡