Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14.
Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14.
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DOI：
10.1038/s41467-021-23581-3
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发表时间：
2021-06-15
影响因子：
16.6
通讯作者：
Sosa H
中科院分区：
文献类型：
--
作者：
Benoit MPMH;Asenjo AB;Paydar M;Dhakal S;Kwok BH;Sosa H
KIF 14是一种有丝分裂驱动蛋白，其功能障碍与大脑和肾脏发育缺陷以及几种癌症有关。像其他驱动蛋白一样，KIF 14将ATP水解和微管结合耦合到机械功的产生，但这些过程之间的耦合机制仍然不完全清楚。在这里，我们报告了20个高分辨率（2.7-3.9 μ m）冷冻电子显微镜KIF 14-微管结构与互补功能测定。实施分析程序以分离微管结合的单体和二聚体KIF 14构建体的共存构象。这些数据提供了微管和核苷酸诱导的KIF 14构象变化的全面视图。它表明：1）微管结合、核苷酸种类和颈连接结构域控制马达结构域的三种主要构象之间的转变; 2）未对接的颈连接体阻止核苷酸结合口袋完全闭合并抑制ATP水解; 3）需要13个颈连接体残基来呈现稳定的对接构象; 5）当与微管结合时，KIF 14二聚体的两个马达结构域采用不同的构象;和6）双头结合态的形成在KIF 14二聚体的两个马达域中引入结构变化。这些观察结果提供了一个协调的化学机械驱动蛋白易位模型的结构基础。KIF 14是一种有丝分裂驱动蛋白，其功能障碍与大脑和肾脏发育缺陷以及几种癌症有关。在这里，作者使用cryoEM来确定在不同核苷酸类似物存在下与微管结合的KIF 14构建体的20种结构，并为协调的化学机械驱动蛋白易位模型提供结构基础。
KIF14 is a mitotic kinesin whose malfunction is associated with cerebral and renal developmental defects and several cancers. Like other kinesins, KIF14 couples ATP hydrolysis and microtubule binding to the generation of mechanical work, but the coupling mechanism between these processes is still not fully clear. Here we report 20 high-resolution (2.7–3.9 Å) cryo-electron microscopy KIF14-microtubule structures with complementary functional assays. Analysis procedures were implemented to separate coexisting conformations of microtubule-bound monomeric and dimeric KIF14 constructs. The data provide a comprehensive view of the microtubule and nucleotide induced KIF14 conformational changes. It shows that: 1) microtubule binding, the nucleotide species, and the neck-linker domain govern the transition between three major conformations of the motor domain; 2) an undocked neck-linker prevents the nucleotide-binding pocket to fully close and dampens ATP hydrolysis; 3) 13 neck-linker residues are required to assume a stable docked conformation; 4) the neck-linker position controls the hydrolysis rather than the nucleotide binding step; 5) the two motor domains of KIF14 dimers adopt distinct conformations when bound to the microtubule; and 6) the formation of the two-heads-bound-state introduces structural changes in both motor domains of KIF14 dimers. These observations provide the structural basis for a coordinated chemo-mechanical kinesin translocation model. KIF14 is a mitotic kinesin whose malfunction is associated with cerebral and renal developmental defects and several cancers. Here the authors use cryoEM to determine 20 structures of KIF14 constructs bound to microtubules in the presence of different nucleotide analogues and provide the structural basis for a coordinated chemo-mechanical kinesin translocation model.
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影响因子：
5.6
作者：
Arora, Kritica;Talje, Lama;Kwok, Benjamin H.
通讯作者：
Kwok, Benjamin H.
影响因子：
7.7
作者：
Bai, Xiao-chen;Rajendra, Eeson;Scheres, Sjors H. W.
通讯作者：
Scheres, Sjors H. W.
影响因子：
16.8
作者：
Asenjo, Ana B.;Weinberg, Yonatan;Sosa, Hernando
通讯作者：
Sosa, Hernando
影响因子：
7.7
作者：
Andreasson JO;Milic B;Chen GY;Guydosh NR;Hancock WO;Block SM
通讯作者：
Block SM
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH