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对参与刺猬信号通路的驱动蛋白——人类Kif7的结构洞察。

Structural insights into human Kif7, a kinesin involved in Hedgehog signalling.

作者信息

Klejnot Marta, Kozielski Frank

机构信息

The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland.

出版信息

Acta Crystallogr D Biol Crystallogr. 2012 Feb;68(Pt 2):154-9. doi: 10.1107/S0907444911053042. Epub 2012 Jan 13.

Abstract

Kif7, a member of the kinesin 4 superfamily, is implicated in a variety of diseases including Joubert, hydrolethalus and acrocallosal syndromes. It is also involved in primary cilium formation and the Hedgehog signalling pathway and may play a role in cancer. Its activity is crucial for embryonic development. Kif7 and Kif27, a closely related kinesin in the same subfamily, are orthologues of the Drosophila melanogaster kinesin-like protein Costal-2 (Cos2). In vertebrates, they work together to fulfil the role of the single Cos2 gene in Drosophila. Here, the high-resolution structure of the human Kif7 motor domain is reported and is compared with that of conventional kinesin, the founding member of the kinesin superfamily. These data are a first step towards structural characterization of a kinesin-4 family member and of this interesting molecular motor of medical significance.

摘要

驱动蛋白4超家族成员Kif7与多种疾病有关,包括乔布综合征、水脑致死综合征和胼胝体发育不全综合征。它还参与初级纤毛的形成和刺猬信号通路,可能在癌症中发挥作用。其活性对胚胎发育至关重要。Kif7和Kif27是同一亚家族中密切相关的驱动蛋白,是果蝇驱动蛋白样蛋白Costal-2(Cos2)的直系同源物。在脊椎动物中,它们共同发挥果蝇中单个Cos2基因的作用。在此,报道了人类Kif7运动结构域的高分辨率结构,并将其与驱动蛋白超家族的创始成员传统驱动蛋白的结构进行了比较。这些数据是对驱动蛋白4家族成员以及这种具有医学意义的有趣分子马达进行结构表征的第一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd17/3266853/96d0f1bb7c5b/d-68-00154-fig1.jpg

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