Cooperative Effects of Cofilin (ADF) on Actin Structure Suggest Allosteric Mechanism of Cofilin Function

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 conformat...

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Bibliographic Details
Published in:Journal of molecular biology 2006-02, Vol.356 (2), p.325-334
Main Authors: Bobkov, Andrey A., Muhlrad, Andras, Pavlov, Dmitry A., Kokabi, Kaveh, Yilmaz, Atilgan, Reisler, Emil
Format: Article
Language:English
Subjects:
actin
Actin Depolymerizing Factors - chemistry
Actin Depolymerizing Factors - metabolism
Actins - chemistry
Actins - metabolism
ADF
Allosteric Regulation
Animals
Calorimetry, Differential Scanning
cofilin
cooperativity
Disulfides - chemistry
DSC
Models, Molecular
Protein Conformation
Rabbits
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Summary: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.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2005.11.072