Analysis of the human cofilin 1 structure reveals conformational changes required for actin binding

KlejnotM.; GabrielsenM.; CameronJ.MleczakA.TalapatraS.K.KozielskiF.PanniferA.OlsonM.F.

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Analysis of the human cofilin 1 structure reveals conformational changes required for actin binding

机译：分析揭示了人类cofilin 1的结构肌动蛋白构象变化需要绑定

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The actin cytoskeleton is the chassis that gives a cell its shape and structure, and supplies the power for numerous dynamic processes including motility, endocytosis, intracellular transport and division. To perform these activities, the cytoskeleton undergoes constant remodelling and reorganization. One of the major actin-remodelling families are the cofilin proteins, made up of cofilin 1, cofilin 2 and actin-depolymerizing factor (ADF), which sever aged ADP-associated actin filaments to reduce filament length and provide new potential nucleation sites. Despite the significant interest in cofilin as a central node in actin-cytoskeleton dynamics, to date the only forms of cofilin for which crystal structures have been solved are from the yeast, Chromalveolata and plant kingdoms; none have previously been reported for an animal cofilin protein. Two distinct regions in animal cofilin are significantly larger than in the forms previously crystallized, suggesting that they would be uniquely organized. Therefore, it was sought to determine the structure of human cofilin 1 by X-ray crystallography to elucidate how it could interact with and regulate dynamic actin-cytoskeletal structures. Although wild-type human cofilin 1 proved to be recalcitrant, a C147A point mutant yielded crystals that diffracted to 2.8? resolution. These studies revealed how the actin-binding helix undergoes a conformational change that increases the number of potential hydrogen bonds available for substrate binding.

机译：肌动蛋白细胞骨架是给底盘细胞的形状和结构,和供应许多动态过程包括能动性,内吞作用,细胞内运输和分裂。细胞骨架发生不断的改造和重组。actin-remodelling cofilin家庭蛋白质,由cofilin 1, cofilin 2actin-depolymerizing因素(ADF),切断岁ADP-associated肌动蛋白丝减少纤维长度和提供新的潜力成核的网站。cofilin作为中心节点的兴趣actin-cytoskeleton动力学,迄今为止唯一形式的cofilin晶体结构从酵母已经解决了,Chromalveolata和植物王国;此前报道的动物cofilin蛋白质。明显大于在形式先前结晶,建议他们将独特的组织。试图确定人类的结构cofilin 1 x射线晶体学来阐明如何使用和管理动态互动actin-cytoskeletal结构。人类cofilin 1证明是顽固的,C147A点突变产生晶体衍射到2.8吗?揭示了actin-binding螺旋经历构象变化,增加了数量可用的潜在的氢键衬底绑定。

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《Acta crystallographica.Section D. Biological crystallography》 |2013年第9期|1780-1788|共9页
作者
KlejnotM.; GabrielsenM.; CameronJ.MleczakA.TalapatraS.K.KozielskiF.PanniferA.OlsonM.F.;
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Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, United;

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正文语种英语
中图分类化学;
关键词
Cytoskeleton; Chassis Device Component; Actin CytoskeletonCofilin 1CFL1 genecofilinSet of central axillary lymph nodesActins;

机译：细胞骨架,底盘设备组件;肌动蛋白CytoskeletonCofilin 1CFL1 genecofilinSet或中央腋窝淋巴nodesActins;

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Analysis of the human cofilin 1 structure reveals conformational changes required for actin binding

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