FREE ENERGY CONVERSION IN BIOLOGY

生物学中的自由能量转换

• 批准号: 6161940
• 负责人: Yin-Ching Iris Chen
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161940
• 关键词: active transport; bioenergetics; biophysics; catalyst; chemical models; electric field; enzyme activity; hydrolysis; kinesin; microtubules; thermodynamics

This is a continuation of last year's work on the mechanisms of movement of the motor protein kinesin on a microtubule (a periodic biopolymer made of identical monomer subunits). A single kinesin molecule when attached to a microscopic plastic bead can move itself and carry the bead with it unidirectionally on a microtubule by catalyzing the hydrolysis of ATP. The movement can be carried out by both one-headed and two-headed kinesin molecules. In the two-headed case, the simplest mechanism for movement is the so-called "hand-over-hand" model, in which the two heads alternate between attached and detached states in an ordered sequence (like the walking motion of a human being). Exactly how a one-headed kinesin moves the bead is not clear. Our research in this year was centered on this question. Our research has yielded two findings. First, using the theory of "cross-bridge" formalism for muscle contraction, we have found that the movement of a bead on a microtubule powered by a single one-headed kinesin is equivalent to the movement of a Brownian particle in a fluctuating periodic potential field. Therefore, the first step in understanding the mechanism of kinesin movement is to solve the Brownian motion problem. The movement of a Brownian particle in a fluctuating periodic potential field has been solved before for the case that the potential within each period is asymmetric. For biological motors, the potential is symmetric. No studies of this kind on symmetric potentials have been reported up to now. We are the first to solve this problem. We have found that, in order for a Brownian particle to execute a biased movement in a fluctuating periodic symmetric potential, the following two conditions have to be satisfied. First, the potential must fluctuate among three or more translationally-shifted "potential states". Second, the fluctuation process must be done in such a way that a net cycling around the states exists. Using the model we developed, we found that a single one-headed kinesin indeed can move a bead on a microtubule if the kinesin can attached to the microtubule in two distinct conformations with different tilting angles relative to the axis of the microtubule. We also have developed a formalism for calculating the movement velocity of the particle at long time when the kinetic parameters of the fluctuation process are given. The formalism should be useful in studying in vitro motility measurements in which the bead is powered by one-headed kinesin molecules.

这是去年关于运动机制的工作的继续 微管上的运动蛋白驱动蛋白（一种周期性的生物聚合物 由相同的单体亚基组成）。 一个驱动蛋白分子， 附着在一个微小的塑料珠上， 珠与它单向上的微管通过催化 ATP水解。 运动可以由两个单头 和双头驱动蛋白分子。 在双头的情况下，最简单的 运动的机制是所谓的“手交手”模式，其中， 这两个头在连接和分离状态之间交替， 有序序列（就像人类的行走运动）。 完全 单头驱动蛋白如何移动珠子尚不清楚。 我们的研究 今年就是围绕这个问题， 我们的研究发现了两个 调查结果。 第一，运用“过桥”形式主义理论， 肌肉收缩时，我们发现， 由单个单头驱动蛋白驱动的微管相当于 布朗粒子在涨落周期势场中的运动 领域 因此，理解这种机制的第一步是 驱动蛋白运动是解决布朗运动问题。 运动 布朗粒子在波动的周期性势场中的运动 对于每个周期内的势 是不对称的 对于生物马达，电势是对称的。 没有 这种关于对称势的研究已经报道， 现在 我们是第一个解决这个问题的人。 我们发现，在 布朗粒子在轨道中执行偏置运动的顺序 波动周期对称势，以下两个条件 必须得到满足。 第一，电势必须在三个 或更多的纵向移动的“可能状态”。 二是 波动过程必须以这样一种方式进行， 国家存在。 使用我们开发的模型，我们发现， 单头驱动蛋白确实可以移动微管上的珠子， 驱动蛋白可以两种不同的构象附着在微管上 相对于微管的轴具有不同的倾斜角。 我们还开发了一种计算运动速度的形式主义 当颗粒的动力学参数 波动过程。 形式主义应该是有用的， 研究体外运动性测量，其中珠子由 单头驱动蛋白分子。