Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5711-6. doi: 10.1073/pnas.1116784109. Epub 2012 Mar 26.
The biological functions of coiled coils generally depend on efficient folding and perfect pairing of their α-helices. Dynamic changes in the helical registry that lead to staggered helices have only been proposed for a few special systems and not found in generic coiled coils. Here, we report our observations of multiple staggered helical structures of two canonical coiled coils. The partially folded structures are formed predominantly by coiled coil misfolding and occasionally by helix sliding. Using high-resolution optical tweezers, we characterized their energies and transition kinetics at a single-molecule level. The staggered states occur less than 2% of the time and about 0.1% of the time at zero force. We conclude that dynamic changes in helical registry may be a general property of coiled coils. Our findings should have broad and unique implications in functions and dysfunctions of proteins containing coiled coils.
卷曲螺旋的生物学功能通常依赖于其α-螺旋的有效折叠和完美配对。只有在少数特殊系统中才提出了导致交错螺旋的螺旋排列的动态变化，而在通用卷曲螺旋中并未发现。在这里，我们报告了对两个典型卷曲螺旋的多个交错螺旋结构的观察结果。部分折叠结构主要由卷曲螺旋错误折叠形成，偶尔由螺旋滑动形成。使用高分辨率光镊，我们在单分子水平上对其能量和转变动力学进行了表征。交错状态出现的时间不到 2%，在零力下出现的时间约为 0.1%。我们得出结论，螺旋排列的动态变化可能是卷曲螺旋的普遍特性。我们的发现应该对含有卷曲螺旋的蛋白质的功能和功能障碍具有广泛而独特的意义。
