Biozentrum, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland.
Angew Chem Int Ed Engl. 2018 May 14;57(20):5921-5924. doi: 10.1002/anie.201713064. Epub 2018 Apr 17.
Many molecular chaperones are promiscuous and interact with a wide range of unfolded, quasi-native, and native client proteins. The mechanisms by which chaperones interact with the highly diverse structures of native clients thus remain puzzling. In this work, we investigate at the atomic level how three ATP-independent chaperones interact with a β-sheet-rich protein, the Fyn SH3 domain. The results reveal that the chaperone Spy recognizes the locally frustrated surface of the client Fyn SH3 and that the interaction is transient and highly dynamic, leaving the chaperone-interacting surface on Fyn SH3 solvent accessible. The two alternative molecular chaperones SurA and Skp recognize the same locally frustrated surface of the Fyn SH3 domain. These results indicate dynamic recognition of frustrated segments as a common mechanism underlying the chaperone-native client interaction, which also provides a basis for chaperone promiscuousness.
许多分子伴侣是混杂的，与广泛的未折叠、准天然和天然客户蛋白相互作用。因此，伴侣如何与高度多样化的天然客户结构相互作用仍然令人费解。在这项工作中，我们在原子水平上研究了三种 ATP 非依赖性伴侣如何与富含 β 片层的蛋白质 Fyn SH3 结构域相互作用。结果表明，伴侣 Spy 识别客户 Fyn SH3 的局部受挫表面，并且相互作用是瞬态的和高度动态的，使 Fyn SH3 上的伴侣相互作用表面溶剂可及。两种替代的分子伴侣 SurA 和 Skp 识别 Fyn SH3 结构域的相同局部受挫表面。这些结果表明，受挫片段的动态识别是伴侣-天然客户相互作用的共同机制，这也为伴侣的混杂性提供了基础。
