Maurice Wilkins Centre, School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand.
Maurice Wilkins Centre, School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand.
Structure. 2014 Oct 7;22(10):1433-45. doi: 10.1016/j.str.2014.08.015.
Myxovirus resistance (Mx) proteins restrict replication of numerous viruses. They are closely related to membrane-remodeling fission GTPases, such as dynamin. Mx proteins can tubulate lipids and form rings or filaments that may interact directly with viral structures. GTPase domain dimerization is thought to allow crosstalk between the rungs of a tubular or helical assembly, facilitating constriction. We demonstrate that the GTPase domain of MxA dimerizes to facilitate catalysis, in a fashion analogous to dynamin. GTP binding is associated with the lever-like movement of structures adjacent to the GTPase domain, while GTP hydrolysis returns MxA to its resting state. Dimerization is not significantly promoted by substrate binding and occurs only transiently, yet is central to catalytic efficiency. Therefore, we suggest dimerization functions to coordinate the activity of spatially adjacent Mx molecules within an assembly, allowing their mechanical power strokes to be synchronized at key points in the contractile cycle.
抗病毒蛋白（Mx）能够限制多种病毒的复制。它们与膜重塑分裂 GTP 酶（如 dynamin）密切相关。Mx 蛋白可以使脂质形成小管并形成环或纤维，这些结构可能直接与病毒结构相互作用。GTP 酶结构域二聚化被认为可以在管状或螺旋组装的梯级之间进行交流，从而促进收缩。我们证明，MxA 的 GTP 酶结构域二聚化以促进催化，其方式类似于 dynamin。GTP 结合与 GTP 酶结构域相邻结构的杠杆运动相关，而 GTP 水解将 MxA 返回到其静止状态。底物结合不会显著促进二聚化，并且仅短暂发生，但对催化效率至关重要。因此，我们认为二聚化的功能是协调组装内空间相邻 Mx 分子的活性，允许它们的机械力冲程在收缩周期的关键点上同步。
