Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA.
Mol Cell. 2011 Sep 2;43(5):764-75. doi: 10.1016/j.molcel.2011.07.022.
Metaphase chromosome positioning depends on Kif18A, a kinesin-8 that accumulates at and suppresses the dynamics of K-MT plus ends. By engineering Kif18A mutants that suppress MT dynamics but fail to concentrate at K-MT plus ends, we identify a mechanism that allows Kif18A to accumulate at K-MT plus ends to a level required to suppress chromosome movements. Enrichment of Kif18A at K-MT plus ends depends on its C-terminal tail domain, while the ability of Kif18A to suppress MT growth is conferred by the N-terminal motor domain. The Kif18A tail contains a second MT-binding domain that diffuses along the MT lattice, suggesting that it tethers the motor to the MT track. Consistently, the tail enhances Kif18A processivity and is crucial for it to accumulate at K-MT plus ends. The heightened processivity of Kif18A, conferred by its tail domain, thus promotes concentration of Kif18A at K-MT plus ends, where it suppresses their dynamics to control chromosome movements.
中期染色体定位取决于 Kif18A,它是一种聚集在和抑制 K-MT 正极动力学的驱动蛋白 8。通过工程化 Kif18A 突变体,这些突变体抑制 MT 动力学但不能集中在 K-MT 正极,我们确定了一种机制,允许 Kif18A 积累到足以抑制染色体运动所需的 K-MT 正极。Kif18A 在 K-MT 正极的富集依赖于其 C 末端尾部结构域,而 Kif18A 抑制 MT 生长的能力则由 N 末端的马达结构域赋予。Kif18A 的尾部包含第二个 MT 结合域,该结合域沿着 MT 晶格扩散,表明它将马达固定在 MT 轨道上。一致地,尾部增强了 Kif18A 的进程性,对于其在 K-MT 正极的积累至关重要。尾部赋予 Kif18A 的高进程性,从而促进了 Kif18A 在 K-MT 正极的集中,在那里它抑制它们的动力学以控制染色体运动。