tailieunhanh - Báo cáo khoa học: Co-operation of domain-binding and calcium-binding sites in the activation of gelsolin

Gelsolin is an abundant calcium dependent actin filament severing and capping protein. In the absence of calcium the molecule is compact but in the presence of calcium, as its six similar domains alter their relativeposition, agenerallymore open configuration is adopted to reveal the three actin binding sites. It is generally held that a helical-latch at the C-terminusof gelsolin’sdomain6 (G6), bindsdomain2 (G2) to keep gelsolin in the calcium-free compact state, and that the crutial calcium binding site(s) reside in the C-terminal half of gelsolin perhaps involving the C-terminal helix itself has to be bound to release this latch. . | Eur. J. Biochem. 270 2236-2243 2003 FEBS 2003 doi Co-operation of domain-binding and calcium-binding sites in the activation of gelsolin Emeline Lagarrigue1 Sutherland K. Maciver2 Abdellatif Fattoum3 Yves Benyamin1 and Claude Roustan1 1UMR 5539 CNRS Laboratoire de motilité cellulaire Ecole Pratique des Hautes Etudes Université de Montpellier 2 France 2Genes and Development Group Department of Biomedical Sciences University of Edinburgh Scotland UK 3Centre de Recherches de Biochimie Macromoleculaire UPR 1086 CNRS Montpellier France Gelsolin is an abundant calcium dependent actin filament severing and capping protein. In the absence of calcium the molecule is compact but in the presence of calcium as its six similar domains alter their relative position a generally more open configuration is adopted to reveal the three actin binding sites. It is generally held that a helical-latch at the C-terminus of gelsolin s domain 6 G6 binds domain 2 G2 to keep gelsolin in the calcium-free compact state and that the crutial calcium binding site s reside in the C-terminal half of gelsolin perhaps involving the C-terminal helix itself has to be bound to release this latch. Here we provide evidence for a calcium dependent conformational change within G2 Kd e15 M . We also report a calcium dependent binding site for the C-terminus G4-6 within G2 and delimit this further to a specific region formed by residues 203-225 and 159-193. It is known that the activation of gelsolin involves multiple calcium binding events around 6 the first of which in G6 may release the latch. We propose that the calcium-dependent conformational change in G2 may be a subsequent step that is necessary for the dissociation of G2 from G4-6 and that this movement occurs in sympathy with calcium induced conformational changes within G6 by the physical coupling of the two calcium binding sites within G2 and G6. Additional calcium binding in other domains then result in the .

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