tailieunhanh - Báo cáo khoa học: The activation of gelsolin by low pH The calcium latch is sensitive to calcium but not pH

Gelsolin is a multidomain and multifunction protein that nucleates the assembly of filaments and severs them. The activation of gelsolin by calcium is a multistep process involving many calcium binding sites that act to unfold the molecule from a tight structure to a more loose form in which three actin-binding sites become exposed. Low pHis alsoknowntoactivategelsolin, in theabsenceof calciumand this too results in an unfolding of the molecule. | Eur. J. Biochem. 270 4105-4112 2003 FEBS 2003 doi The activation of gelsolin by low pH The calcium latch is sensitive to calcium but not pH Emeline Lagarrigue1 Diane Ternent2 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 Montpellier Cedex 5 France 2Genes and Development Group Department of Biomedical Sciences University of Edinburgh Hugh Robson Building George Square Edinburgh Scotland 3Centre de Recherches de Biochimie Macromoleculaire UPR 1086 CNRS Montpellier Cedex 5 France Gelsolin is a multidomain and multifunction protein that nucleates the assembly of filaments and severs them. The activation of gelsolin by calcium is a multistep process involving many calcium binding sites that act to unfold the molecule from a tight structure to a more loose form in which three actin-binding sites become exposed. Low pH is also known to activate gelsolin in the absence of calcium and this too results in an unfolding of the molecule. Less is known how pH-activation occurs but we show that there are significant differences in the mechanisms that lead to activation. Crucially while it is known that the bonds between G2 and G6 are broken by co-operative occupancy of calcium binding sites in both domains Lagarrique E. Maciver S. K. Fattoum A. Benyamin Y. Roustan C. 2003 Eur. J. Biochem. 270 2236-2243. pH values that aciivate gelsolin do not result in a weakening of the G2-G6 bonds. We report the existence of pH-dependent conformational changes within G2 and in G4-6 that differ from those induced by calcium and that low pHoverrides the requirement for calcium for actin-binding within G4-6 to a modest extent so that a Kd of 1 IM is measured compared to 30-40 nM in the presence of calcium. Whereas the pH-dependent conformational change in G2 is possibly different from the change induced by calcium the .