Cooperative effects of cofilin (ADF) on actin structure suggest allosteric mechanism of cofilin function

被引:69
作者
Bobkov, AA
Muhlrad, A
Pavlov, DA
Kokabi, K
Yilmaz, A
Reisler, E
机构
[1] Burnham Inst, La Jolla, CA 92037 USA
[2] Hebrew Univ Jerusalem, Sch Dent Med, Inst Dent Sci, IL-91120 Jerusalem, Israel
[3] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
关键词
actin; ADF; cofilin; cooperativity; DSC;
D O I
10.1016/j.jmb.2005.11.072
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:325 / 334
页数:10
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