The Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UK.
Science. 2011 Aug 12;333(6044):883-5. doi: 10.1126/science.1204824.
When not transporting cargo, kinesin-1 is autoinhibited by binding of a tail region to the motor domains, but the mechanism of inhibition is unclear. We report the crystal structure of a motor domain dimer in complex with its tail domain at 2.2 angstroms and compare it with a structure of the motor domain alone at 2.7 angstroms. These structures indicate that neither an induced conformational change nor steric blocking is the cause of inhibition. Instead, the tail cross-links the motor domains at a second position, in addition to the coiled coil. This "double lockdown," by cross-linking at two positions, prevents the movement of the motor domains that is needed to undock the neck linker and release adenosine diphosphate. This autoinhibition mechanism could extend to some other kinesins.
当没有运输货物时，动力蛋白-1通过尾部区域与马达结构域的结合而被自动抑制，但抑制的机制尚不清楚。我们报告了在 2.2 埃分辨率下马达结构域二聚体与其尾部区域复合物的晶体结构，并与在 2.7 埃分辨率下马达结构域单体的结构进行了比较。这些结构表明，抑制既不是诱导构象变化也不是空间位阻的结果。相反，尾部除了卷曲螺旋外，还在第二个位置交联马达结构域。这种“双重锁定”通过在两个位置交联，阻止了马达结构域的运动，而这种运动是解开颈部接头并释放二磷酸腺苷所必需的。这种自动抑制机制可能扩展到其他一些驱动蛋白。
