Abstract
Life is driven by awe-inspiring coordinated movements observed in cells and tissues. In each cell, nm-size molecular motor proteins contribute to these movements as they power numerous mechanical processes with precision and complex orchestration. For the multiple functions that an eukaryotic cell accomplish, motility is essential both at molecular and cellular scales. Tissue morphogenesis, cell migration, cell division or cell differentiation are all controlled by the precise action of such nanomotors that work on cytoskeletal tracks using ATP as fuel. The study of motility has a long history and scientists of all disciplines have contributed to its understanding. The first part of this review compares myosin and kinesin motors to describe the principles underlying how motors convert chemical energy into mechanical movement. In a second part, I will describe how sequence differences selected through evolution can lead to distinct force production output despite a common mechanism. Motors within a superfamily can thus carry out distinct functions in cells. Such differences give rise to their individual, specific motility properties, including reversal of directionality or ability to organize cytoskeletal tracks. The power of structural biology to reveal unexpected and surprising structures, with certainty when visualized at atomic resolution, has been a great advantage for this field. The critical insights gained from the structures can be carefully tested with functional experiments, leading to progress in defining the role motors play in cells. Last, I will describe how targeting these motors can be beneficial for human health. Allosteric sites for specific small molecules can act as activators or inhibitors of the force produced by these nanomotors. While frequent sites of mutations in these motors can lead to disease phenotypes, high therapeutic potential of allosteric effectors is now established for heart muscle diseases and should be extended to treat other pathologies.
Highlights
Motility is an essential property for all living organisms. It critically depends on biological nanomachines called molecular motors
Their capacity to produce uni-directional force or movement within the crowded environment of a cell is essential for cell division, morphogenesis, intracellular trafficking, muscle contraction and numerous specialized cellular functions
The astonishing wealth of biological motors really became obvious in the 90s upon the sequencing of the genomes that lead to the discovery of the myosin and kinesin superfamilies [9, 10]
Summary
Motility is an essential property for all living organisms. It critically depends on biological nanomachines called molecular motors. The astonishing wealth of biological motors really became obvious in the 90s upon the sequencing of the genomes that lead to the discovery of the myosin and kinesin superfamilies [9, 10] All these proteins produce force via their motor domain and mechanical element, while their tail regions are diverse and play essential roles for assembly or recruitment of these motors. The motor domain sequence of different types of myosins, define their individual motor properties that underly their distinct roles in cells How fast they move, how many steps they can perform on a single track prior to detachment (processive movement) and how they can operate under opposite force (load) is important. New effectors that have emerged as promising drug candidates can modulate the force produced by a particular myosin, these will be discussed in the context of how these molecules can be used in targeted and personalized medicine
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