title: Cooperative effects of cofilin (ADF) on actin structure suggest allosteric mechanism of cofilin function.
abstract: 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.
authors.affiliation: The Burnham Institute, La Jolla, CA 92037, USA. abobkov@burnham.org
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Bobkov
authors.forename: Andras
authors.initials: A
authors.lastname: Muhlrad
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Pavlov
authors.forename: Kaveh
authors.initials: K
authors.lastname: Kokabi
authors.forename: Atilgan
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Emil
authors.initials: E
authors.lastname: Reisler
mesh_terms: D051339:Actin Depolymerizing Factors / Q000737:chemistry* / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D002152:Calorimetry, Differential Scanning; D004220:Disulfides / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D011817:Rabbits
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D004220:Disulfides