This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Kinesin is a molecular motor responsible for hauling essential cargoes within cells by walking step by step along filamentous tracks known as microtubules. To move efficiently and avoid falling off, the motor's two feet must coordinate their stepping in a precise direction.
Scientists have known that a connecting segment called the neck region is crucial for coordinating this motion. However, its exact three-dimensional structure and how it physically interacts with the microtubule track have remained a mystery because of the limitations of current imaging techniques. To overcome these limitations, a research team built an atomic-level model of the kinesin motor on a microtubule track—a system of approximately 3 million atoms—and simulated its dynamics on the supercomputer Fugaku.
Using an enhanced-sampling technique called generalized replica exchange with solute tempering (gREST) across two independent computational physics models (force fields), the researchers mapped the flexible neck region to determine its most stable structure. They then simulated the motor's initial stepping motion using a simplified detachment model in which underlying microtubule subunits were removed. The findings are published in the Biophysical Journal.
The simulations revealed a high-confidence structure of the neck region, demonstrating that its twisted two-strand spiral (coiled coil) lies perpendicular to the microtubule and maintains close contact with the track surface. When modeling the motor's stepping motion, the researchers found that physical interactions between the neck and the track surface strongly bias the foot's stepping trajectory. Rather than moving straight over the top of the leading foot, the rear foot swings around the right side of the front foot along a counterclockwise path.
Simulations confirmed that this specific neck-track interaction is required for forward movement, as alternative neck configurations with weak track interactions failed to step forward. These findings explain how kinesin steers its steps at the atomic level. By resolving how local structural elements regulate movement directionality, this study offers a vital foundation for advancing the understanding of cellular transport.
The authors also note the study's next challenges, which arise from three simplifications in the current model: the use of a truncated kinesin construct, the artificial removal of microtubule subunits to trigger a step, and the omission of flexible structural elements (E-hooks) on the microtubule surface. Future studies incorporating full-length kinesin constructs and flexible track elements will further refine this structural framework. Song-Ho Chong et al, Neck region-microtubule interactions direct counterclockwise stepping of kinesin-1, Biophysical Journal (2026).
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