title: The identification of a second cofilin binding site on actin suggests a novel, intercalated arrangement of F-actin binding.
abstract: The cofilins are members of a protein family that binds monomeric and filamentous actin, severs actin filaments, and increases monomer off-rate from the pointed end. Here, we characterize the cofilin-actin interface. We confirm earlier work suggesting the importance of the lower region of subdomain 1 encompassing the N and C termini (site 1) in cofilin binding. In addition, we report the discovery of a new cofilin binding site (site 2) from residues 112-125 that form a helix toward the upper, rear surface of subdomain 1 in the standard actin orientation (Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., and Holmes, K. C. (1990) Nature 347, 37-44). We propose that cofilin binds "behind" one monomer and "in front" of the other longitudinally associated monomer, accounting for the fact that cofilin alters the twist in the actin (McGough, A., Pope, B., Chiu, W., and Weeds, A. (1997) J. Cell Biol. 138, 771-781). The characterization of the cofilin-actin interface will facilitate an understanding of how cofilin severs and depolymerizes filaments and may shed light on the mechanism of the gelsolin family because they share a similar fold with the cofilins (Hatanaka, H., Ogura, K., Moriyama, K., Ichikawa, S., Yahara, I., and Inagiki, F. (1996) Cell 85, 1047-1055).
authors.affiliation: UMR 5539 (CNRS), Laboratoire de Motilité Cellulaire (Ecole Pratique des Hautes Etudes), Université de Montpellier 2, Place E. Bataillon, CC107, 34095 Montpellier Cedex 5, France.
authors.forename: C
authors.initials: C
authors.lastname: Renoult
authors.forename: D
authors.initials: D
authors.lastname: Ternent
authors.forename: S K
authors.initials: SK
authors.lastname: Maciver
authors.forename: A
authors.initials: A
authors.lastname: Fattoum
authors.forename: C
authors.initials: C
authors.lastname: Astier
authors.forename: Y
authors.initials: Y
authors.lastname: Benyamin
authors.forename: C
authors.initials: C
authors.lastname: Roustan
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002942:Circular Dichroism; D004926:Escherichia coli; D005454:Fluorescence Polarization; D018260:Gelsolin / Q000737:chemistry; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry*; D018482:Muscle, Skeletal / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D000906:Antibodies; D018260:Gelsolin; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D014364:Tryptophan