Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Sci Adv. 2016 Nov 16;2(11):e1601625. doi: 10.1126/sciadv.1601625. eCollection 2016 Nov.
Molecular chaperones are essential in aiding client proteins to fold into their native structure and in maintaining cellular protein homeostasis. However, mechanistic aspects of chaperone function are still not well understood at the atomic level. We use nuclear magnetic resonance spectroscopy to elucidate the mechanism underlying client recognition by the adenosine triphosphate-independent chaperone Spy at the atomic level and derive a structural model for the chaperone-client complex. Spy interacts with its partially folded client Im7 by selective recognition of flexible, locally frustrated regions in a dynamic fashion. The interaction with Spy destabilizes a partially folded client but spatially compacts an unfolded client conformational ensemble. By increasing client backbone dynamics, the chaperone facilitates the search for the native structure. A comparison of the interaction of Im7 with two other chaperones suggests that the underlying principle of recognizing frustrated segments is of a fundamental nature.
分子伴侣在帮助客户蛋白折叠成天然结构和维持细胞蛋白平衡方面至关重要。然而，在原子水平上，伴侣蛋白的作用机制仍未得到很好的理解。我们使用核磁共振波谱技术在原子水平上阐明了无 ATP 依赖的伴侣蛋白 Spy 识别客户蛋白的机制，并推导出伴侣蛋白-客户蛋白复合物的结构模型。Spy 通过动态选择性识别柔性、局部受阻区域来与部分折叠的客户蛋白 Im7 相互作用。与 Spy 的相互作用使部分折叠的客户蛋白不稳定，但使未折叠的客户蛋白构象集在空间上更加紧凑。通过增加客户蛋白的骨架动力学，伴侣蛋白促进了对天然结构的搜索。Im7 与另外两种伴侣蛋白的相互作用比较表明，识别受阻片段的基本原理具有基础性。
