Distinct conformations of the kinesin Unc104 neck regulate a monomer to dimer motor transition.
Distinct conformations of the kinesin Unc104 neck regulate a monomer to dimer motor transition.
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DOI：
10.1083/jcb.200308020
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发表时间：
2003-11-24
期刊：
影响因子：
--
通讯作者：
Milligan RA
中科院分区：
文献类型：
--
作者：
Al-Bassam J;Cui Y;Klopfenstein D;Carragher BO;Vale RD;Milligan RA
秀丽隐杆线虫Unc104运动蛋白快速运输突触小泡。Unc104在溶液中主要是单体，但最近的运动性研究表明，当它集中在膜上时，它可能会发生二聚。利用冷冻电子显微镜，我们观察到微管结合的Unc104的两种构象：一种是两个颈部螺旋形成分子内平行螺旋的单体状态，另一种是颈部螺旋形成分子间螺旋的二聚体状态。通过删除分隔颈部螺旋的柔性铰链，分子内折叠构象被取消，这表明它作为间隔物来适应平行的盘绕构型。颈部铰链缺失突变不改变体外运动速度，但在转基因线虫中产生严重的不协调表型，提示折叠构象在运动调节中起重要作用。我们认为，Unc104颈部通过从自我折叠、抑制状态转换到支持快速前进运动的二聚化构象来调节运动。
Caenhorhabditis elegans Unc104 kinesin transports synaptic vesicles at rapid velocities. Unc104 is primarily monomeric in solution, but recent motility studies suggest that it may dimerize when concentrated on membranes. Using cryo-electron microscopy, we observe two conformations of microtubule-bound Unc104: a monomeric state in which the two neck helices form an intramolecular, parallel coiled coil; and a dimeric state in which the neck helices form an intermolecular coiled coil. The intramolecular folded conformation is abolished by deletion of a flexible hinge separating the neck helices, indicating that it acts as a spacer to accommodate the parallel coiled-coil configuration. The neck hinge deletion mutation does not alter motor velocity in vitro but produces a severe uncoordinated phenotype in transgenic C. elegans, suggesting that the folded conformation plays an important role in motor regulation. We suggest that the Unc104 neck regulates motility by switching from a self-folded, repressed state to a dimerized conformation that can support fast processive movement.
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