Structural Correlation of the Neck Coil with the Coiled-coil (CC1)-Forkhead-associated (FHA) Tandem for Active Kinesin-3 KIF13A
Structural Correlation of the Neck Coil with the Coiled-coil (CC1)-Forkhead-associated (FHA) Tandem for Active Kinesin-3 KIF13A
复制标题
活性驱动蛋白 3 KIF13A 的颈部线圈与卷曲线圈 (CC1)-叉头相关 (FHA) 串联的结构相关性
DOI：
10.1074/jbc.m115.689091
复制
发表时间：
2016-02-12
影响因子：
4.8
通讯作者：
Feng, Wei
中科院分区：
文献类型：
--
作者：
Ren, Jinqi;Huo, Lin;Feng, Wei
进行性驱动蛋白马达通常包含控制方向性和进行性的螺旋颈。然而，驱动蛋白-3的颈螺旋（NC）太短而不能形成稳定的卷曲螺旋二聚体。在这里，我们发现驱动蛋白-3 KIF 13 A的卷曲螺旋（CC 1）-叉头相关（FHA）串联（通过Pro-390连接到NC）组装为扩展的二聚体。随着Pro-390的去除，KIF 13 A的NC-CC 1串联体意外地形成连续的卷曲螺旋二聚体，其可以很好地对齐到CC 1-FHA二聚体中。Pro-390的反向引入破坏了NC-CC 1卷曲螺旋二聚体，但提供了将NC与CC 1-FHA串联体偶联的内在灵活性。NC、CC 1或FHA结构域的突变均显著损害运动活动。因此，KIF 13 A的NC-CC 1-FHA串联内的三个元件在结构上相互关联以形成用于激活马达的稳定二聚体。这项工作也提供了第一个直接的结构证据来支持一个卷曲螺旋颈部的短特征颈部结构域的驱动蛋白3的形成。
Processive kinesin motors often contain a coiled-coil neck that controls the directionality and processivity. However, the neck coil (NC) of kinesin-3 is too short to form a stable coiled-coil dimer. Here, we found that the coiled-coil (CC1)-forkhead-associated (FHA) tandem (that is connected to NC by Pro-390) of kinesin-3 KIF13A assembles as an extended dimer. With the removal of Pro-390, the NC-CC1 tandem of KIF13A unexpectedly forms a continuous coiled-coil dimer that can be well aligned into the CC1-FHA dimer. The reverse introduction of Pro-390 breaks the NC-CC1 coiled-coil dimer but provides the intrinsic flexibility to couple NC with the CC1-FHA tandem. Mutations of either NC, CC1, or the FHA domain all significantly impaired the motor activity. Thus, the three elements within the NC-CC1-FHA tandem of KIF13A are structurally interrelated to form a stable dimer for activating the motor. This work also provides the first direct structural evidence to support the formation of a coiled-coil neck by the short characteristic neck domain of kinesin-3.