Cooperative effects of cofilin (ADF) on actin structure suggest allosteric mechanism of cofilin function
Cooperative effects of cofilin (ADF) on actin structure suggest allosteric mechanism of cofilin function
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DOI：
10.1016/j.jmb.2005.11.072
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发表时间：
2006-02-17
影响因子：
5.6
通讯作者：
Reisler, E
中科院分区：
文献类型：
--
作者：
Bobkov, AA;Muhlrad, A;Reisler, E
利用定点荧光探针和交联剂，我们证明了肌动蛋白细胞动力学的关键调节因子--粘附素(ADF)以合作的方式削弱了F-肌动蛋白的纵向接触。差示扫描量热法检测到粘附素对F-肌动蛋白构象的双重影响。在亚化学计量比的粘附素与肌动蛋白的比例下，粘附点的粘附素以立体和非协同方式稳定，而在F-肌动蛋白的非粘附性部分以变构和协同方式使原体失稳。这种破坏稳定的效应具有很长的范围，一个Cofilin分子影响100多个原核分子，并且在Cofilin与肌动蛋白的摩尔比约为1：2时，其浓度依赖的幅度达到最大。与现有的模型不同，我们的结果表明肌动蛋白解聚是一种变构机制。我们认为，cofilin不太可能像以前认为的那样，在连接点切断肌动蛋白细丝。相反，由于它的双重结构效应，自发断裂最有可能发生在被附近的Cofilin分子变构削弱的无Cofilin的细丝片段中。(C)2005爱思唯尔有限公司。保留所有权利。
Using site-specific fluorescence probes and cross-linking we demonstrated that cofilin (ADF), a key regulator of actin cellular dynamics, weakens longitudinal contacts in F-actin in a cooperative manner. Differential scanning calorimetry detected a dual nature of cofilin effects on F-actin conformation. At sub-stoichiometric cofilin to actin ratios, cofilin stabilized sterically and non-cooperatively protomers at the points of attachment, and destabilized allosterically and cooperatively protomers in the cofilin-free parts of F-actin. This destabilizing effect had a long range, with one cofilin molecule affecting more than 100 protomers, and concentration-dependent amplitude that reached maximum at about 1:2 molar ratio of cofilin to actin. In contrast to existing models, our results suggest an allosteric mechanism of actin depolymerization by cofilin. We propose that cofilin is less likely to sever actin filaments at the points of attachment as thought previously. Instead, due to its dual structural effect, spontaneous fragmentation occurs most likely in cofilin-free segments of filaments weakened allosterically by nearby cofilin molecules. (c) 2005 Elsevier Ltd. All rights reserved.