Molecular mechanism for kinesin-1 direct membrane recognition
Molecular mechanism for kinesin-1 direct membrane recognition
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DOI：
10.1101/2021.01.20.427326
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发表时间：
2021-01
期刊：
影响因子：
13.6
通讯作者：
Zuriñe Antón;Johannes F. Weijman;Christopher Williams;E. R. Moody;J. Mantell;Y. Yip;Jessica A. Cross;T. Williams;R. Steiner;M. Crump;D. Woolfson;M. P. Dodding
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文献类型：
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作者：
Zuriñe Antón;Johannes F. Weijman;Christopher Williams;E. R. Moody;J. Mantell;Y. Yip;Jessica A. Cross;T. Williams;R. Steiner;M. Crump;D. Woolfson;M. P. Dodding
驱动蛋白-1使用膜诱导的曲率敏感的两亲性螺旋直接结合到货物膜。在进化过程中，细胞骨架马达蛋白的货物结合能力通过基因复制和选择性剪接得到了扩展。对于微管马达的驱动蛋白-1家族的轻链，这导致了一系列未知分子功能的羧基末端结构域序列。在这里，生物物理，生物化学和细胞生物学方法相结合的系统发育分析，我们确定了一个高度保守的膜诱导的曲率敏感的两亲性螺旋内的一个子集的长驱动蛋白轻链旁系同源物和剪接异构体的这个区域。该螺旋介导驱动蛋白-1与脂质膜的直接结合。膜结合需要特定的阴离子磷脂，并且它有助于驱动蛋白-1依赖性溶酶体定位，这是一种典型的活性，到目前为止，它仅被归因于细胞器相关货物衔接蛋白的识别。这使我们提出了一个蛋白质-脂质重合检测框架驱动蛋白-1介导的细胞器运输。
Kinesin-1 uses a membrane-induced curvature-sensitive amphipathic helix to bind directly to cargo membranes. The cargo-binding capabilities of cytoskeletal motor proteins have expanded during evolution through both gene duplication and alternative splicing. For the light chains of the kinesin-1 family of microtubule motors, this has resulted in an array of carboxyl-terminal domain sequences of unknown molecular function. Here, combining phylogenetic analyses with biophysical, biochemical, and cell biology approaches, we identify a highly conserved membrane-induced curvature-sensitive amphipathic helix within this region of a subset of long kinesin light-chain paralogs and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids, and it contributes to kinesin-1–dependent lysosome positioning, a canonical activity that, until now, has been attributed exclusively the recognition of organelle-associated cargo adaptor proteins. This leads us to propose a protein-lipid coincidence detection framework for kinesin-1–mediated organelle transport.