title: Capping and dynamic relation between domains 1 and 2 of gelsolin.
abstract: Gelsolin is a protein that severs and caps actin filaments. The two activities are located in the N-terminal half of the gelsolin molecules. Severing and subsequent capping requires the binding of domains 2 and 3 (S2-3) to the side of the filaments to position the N-terminal domain 1 (S1) at the barbed end of actin (actin subdomains 1 and 3). The results provide a structural basis for the gelsolin capping mechanism. The effects of a synthetic peptide derived from the sequence of a binding site located in gelsolin S2 on actin properties have been studied. CD and IR spectra indicate that this peptide presented a secondary structure in solution which would be similar to that expected for the native full length gelsolin molecule. The binding of the synthetic peptide induces conformational changes in actin subdomain 1 and actin oligomerization. An increase in the polymerization rate was observed, which could be attributed to a nucleation kinetics effect. The combined effects of two gelsolin fragments, the synthetic peptide derived from an S2 sequence and the purified segment 1 (S1), were also investigated as a molecule model. The two fragments induced nucleation enhancement and inhibited actin depolymerization, two characteristic properties of capping. In conclusion, for the first time it is reported that the binding of a small synthetic fragment is sufficient to promote efficient capping by S1 at the barbed end of actin filaments.
authors.affiliation: Centre de Recherches de Biochimie Macromoléculaire du CNRS, UMR5539, Laboratoire de Recherche sur la Motilité Cellulaire (EPHE), Montpellier, France.
authors.forename: J
authors.initials: J
authors.lastname: Feinberg
authors.forename: O
authors.initials: O
authors.lastname: Kwiatek
authors.forename: C
authors.initials: C
authors.lastname: Astier
authors.forename: S
authors.initials: S
authors.lastname: Diennet
authors.forename: J
authors.initials: J
authors.lastname: Mery
authors.forename: F
authors.initials: F
authors.lastname: Heitz
authors.forename: Y
authors.initials: Y
authors.lastname: Benyamin
authors.forename: C
authors.initials: C
authors.lastname: Roustan
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D018260:Gelsolin / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011817:Rabbits; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D014364:Tryptophan / Q000378:metabolism; D014783:Viscosity
chemical_list: D000199:Actins; D018260:Gelsolin; D010446:Peptide Fragments; D014364:Tryptophan