Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2116-21. doi: 10.1073/pnas.1321022111. Epub 2014 Jan 27.
Myosins are molecular motors that power diverse cellular processes, such as rapid organelle transport, muscle contraction, and tension-sensitive anchoring. The structural adaptations in the motor that allow for this functional diversity are not known, due, in part, to the lack of high-resolution structures of highly tension-sensitive myosins. We determined a 2.3-Å resolution structure of apo-myosin-Ib (Myo1b), which is the most tension-sensitive myosin characterized. We identified a striking unique orientation of structural elements that position the motor's lever arm. This orientation results in a cavity between the motor and lever arm that holds a 10-residue stretch of N-terminal amino acids, a region that is divergent among myosins. Single-molecule and biochemical analyses show that the N terminus plays an important role in stabilizing the post power-stroke conformation of Myo1b and in tuning the rate of the force-sensitive transition. We propose that this region plays a general role in tuning the mechanochemical properties of myosins.
肌球蛋白是一种分子马达，能够驱动多种细胞过程，如快速细胞器运输、肌肉收缩和张力敏感的锚定。由于缺乏高度张力敏感肌球蛋白的高分辨率结构，因此尚不清楚导致这种功能多样性的马达结构适应性。我们确定了apo-myosin-Ib（Myo1b）的 2.3-Å 分辨率结构，Myo1b 是特征最明显的张力敏感肌球蛋白。我们发现了一个引人注目的结构元素的独特取向，它定位了马达的杠杆臂。这种取向导致了在马达和杠杆臂之间形成一个空腔，其中包含一个 10 个残基的 N 端氨基酸延伸，该区域在肌球蛋白中是不同的。单分子和生化分析表明，N 端在稳定 Myo1b 的后动力冲程构象和调节力敏感转换的速率方面起着重要作用。我们提出，该区域在调节肌球蛋白的机械化学性质方面发挥着一般作用。
