Department of Physics, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
J Biol Phys. 2024 Dec;50(3-4):307-325. doi: 10.1007/s10867-024-09661-7. Epub 2024 Jul 30.
During the asymmetric loop extrusion of DNA by a condensin complex, one domain of the complex stably anchors to the DNA molecule, and another domain reels in the DNA strand into a loop. The DNA strand in the loop is fully relaxed, or there is no tension in the loop. Just outside of the loop, there is a tension that resists the extrusion of DNA. To maintain the extrusion of the DNA loop, the condensin complex must have a domain capable of generating a force to overcome the tension outside of the loop. This study proposes that the groove-shaped HEAT repeat domain Ycg1 plays the role of a molecular motor. A DNA molecule may bind to the groove electrostatically, and the weak binding force facilitates the random thermal motion of DNA molecules. A mechanical model that random collisions between DNA and the nonparallel inner surfaces of the groove may generate a directional force which is required for the loop extrusion to sustain. The hinge domain binds to the DNA molecule and acts as an anchor during asymmetric DNA loop extrusion. When the effects of ATP hydrolysis and the viscous drag of the fluid environment are considered, the motor-anchor model for the condensin complex and the mechanical model might explain the asymmetric loop extrusion, the formation of steps, the step size distribution in the loop extrusion, the tension-dependent extrusion speed, the interaction between coexisting loops on the DNA strand, and untying the knots during extrusion. This model can also explain the observed formation of the Z-loop.
在凝聚蛋白复合物对 DNA 进行不对称环挤压的过程中,复合物的一个结构域稳定地锚定在 DNA 分子上,而另一个结构域将 DNA 链卷入环中。环中的 DNA 链完全松弛,或者环中没有张力。就在环外,存在抵抗 DNA 挤出的张力。为了维持 DNA 环的挤出,凝聚蛋白复合物必须具有产生力的结构域以克服环外的张力。本研究提出,槽形 HEAT 重复结构域 Ycg1 充当分子马达的作用。DNA 分子可能通过静电结合到凹槽中,弱结合力促进 DNA 分子的随机热运动。一种机械模型认为,DNA 与凹槽的非平行内表面之间的随机碰撞可能会产生一种定向力,这种力是环挤出维持所必需的。铰链结构域结合到 DNA 分子上,并在不对称 DNA 环挤出过程中充当锚点。当考虑到 ATP 水解的影响和流体环境的粘性阻力时,该马达-锚模型可以解释凝聚蛋白复合物的不对称环挤出、台阶的形成、环挤出过程中的台阶大小分布、依赖张力的挤出速度、共存环在 DNA 链上的相互作用以及挤出过程中解开结的现象。该模型还可以解释观察到的 Z 环的形成。