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分歧的有丝分裂运动蛋白 MKLP2 表现出非典型的结构和机械化学性质。

The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry.

机构信息

Institute of Structural and Molecular Biology, Birkbeck College, London, United Kingdom.

Structural Motility, Institut Curie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Paris, France.

出版信息

Elife. 2017 Aug 11;6:e27793. doi: 10.7554/eLife.27793.

DOI:10.7554/eLife.27793
PMID:28826477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5602324/
Abstract

MKLP2, a kinesin-6, has critical roles during the metaphase-anaphase transition and cytokinesis. Its motor domain contains conserved nucleotide binding motifs, but is divergent in sequence (35% identity) and size (40% larger) compared to other kinesins. Using cryo-electron microscopy and biophysical assays, we have undertaken a mechanochemical dissection of the microtubule-bound MKLP2 motor domain during its ATPase cycle, and show that many facets of its mechanism are distinct from other kinesins. While the MKLP2 neck-linker is directed towards the microtubule plus-end in an ATP-like state, it does not fully dock along the motor domain. Furthermore, the footprint of the MKLP2 motor domain on the MT surface is altered compared to motile kinesins, and enhanced by kinesin-6-specific sequences. The conformation of the highly extended loop6 insertion characteristic of kinesin-6s is nucleotide-independent and does not contact the MT surface. Our results emphasize the role of family-specific insertions in modulating kinesin motor function.

摘要

MKLP2 是一种驱动蛋白-6，在中期-后期转换和胞质分裂过程中具有关键作用。它的马达结构域包含保守的核苷酸结合基序，但与其他驱动蛋白相比，其序列（35%的同源性）和大小（40%更大）存在差异。我们使用低温电子显微镜和生物物理测定法，对微管结合的 MKLP2 马达结构域在其 ATP 酶循环中的机械化学进行了剖析，并表明其许多机制方面都与其他驱动蛋白不同。虽然在 ATP 样状态下，MKLP2 的颈连接子朝向微管的正极，但它并没有完全沿着马达结构域停靠。此外，与运动驱动蛋白相比，MKLP2 马达结构域在 MT 表面上的足迹发生了改变，并被驱动蛋白-6 特异性序列增强。高度延伸的 loop6 插入的构象对核苷酸是不依赖的，并且不与 MT 表面接触。我们的结果强调了家族特异性插入在调节驱动蛋白马达功能方面的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/feaa37b94b7a/elife-27793-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/b86741a54b49/elife-27793-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/1f64b84f33b7/elife-27793-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/dfc7f4aae39e/elife-27793-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/03360475185f/elife-27793-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/7a6ed7318937/elife-27793-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/3c6956503664/elife-27793-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/1a119d2c6639/elife-27793-fig2-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/fba8af1f28cd/elife-27793-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/1ae057a2e838/elife-27793-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/5147979a5381/elife-27793-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/84ccf16429ef/elife-27793-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/16f239e15aee/elife-27793-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/061251b203ae/elife-27793-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/feaa37b94b7a/elife-27793-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/b86741a54b49/elife-27793-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/1f64b84f33b7/elife-27793-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/dfc7f4aae39e/elife-27793-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/03360475185f/elife-27793-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/7a6ed7318937/elife-27793-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/3c6956503664/elife-27793-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/1a119d2c6639/elife-27793-fig2-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/fba8af1f28cd/elife-27793-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/1ae057a2e838/elife-27793-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/5147979a5381/elife-27793-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/84ccf16429ef/elife-27793-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/16f239e15aee/elife-27793-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/061251b203ae/elife-27793-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/5602324/feaa37b94b7a/elife-27793-fig4-figsupp2.jpg

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