Data from: A mathematical understanding of how cytoplasmic dynein walks on microtubules

Cytoplasmic dynein 1 is a dimeric motor protein that walks and transports intracellular cargos towards the minus end of microtubules. In this article we formulate, based on physical principles, a mechanical model to describe the stepping behaviour of cytoplasmic dynein walking on microtubules from the cell membrane towards the nucleus. Unlike previous studies on physical models of this nature, we base our formulation on the whole structure of cytoplasmic dynein 1 to include the temporal dynamics of the individual subunits such as the cargo (for example an endosome, vesicle or bead), two rings of six ATPase domains associated with diverse cellular activities (AAA+ rings) and the microtubule binding domains which allow dynein to bind to microtubules. This mathematical framework allows us to examine experimental observations on dynein across a wide range of different species, as well as being able to make predictions on the temporal behaviour of the individual components of dynein not currently experimentally measured. Furthermore, we extend the model framework to include backward stepping, variable step size and dwelling. The power of our model is in its predictive nature; first it reflects recent experimental observations that dynein walks on microtubules using a weakly coordinated stepping pattern with predominantly not passing steps. Second, the model predicts that interhead coordination in the ATP cycle of cytoplasmic dynein is important in order to obtain the alternating stepping patterns and long run lengths seen in experiments.

细胞质动力蛋白1（Cytoplasmic dynein 1）是一种二聚体动力蛋白，可沿微管（microtubules）向负极移动并转运细胞内货物。本文基于物理原理构建力学模型，用于描述细胞质动力蛋白1在从细胞膜向细胞核延伸的微管上的步进行为。与既往同类物理模型研究不同，本研究以该蛋白的完整结构为基础，纳入了各类单个亚基的时间动力学特性，包括货物（如内体、囊泡或微球）、两个各由六个ATP酶结构域组成的AAA+环（ATPases Associated with diverse cellular Activities），以及介导动力蛋白结合微管的微管结合结构域（microtubule binding domains）。该数学框架不仅可用于分析跨多种物种的动力蛋白实验观测结果，还能预测当前尚未通过实验测得的动力蛋白各组分的时间行为。此外，本文还将该模型框架拓展至涵盖反向步进、可变步长与驻留行为。本模型的核心价值在于其预测性：其一，它契合近期实验观测结果，即细胞质动力蛋白1以弱协调步进模式在微管上运动，且主要不发生跨越步进；其二，模型预测，细胞质动力蛋白ATP循环中的头间协调，对于实现实验中观察到的交替步进模式与长行进距离至关重要。