Berlin 2005 – wissenschaftliches Programm
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AKB: Biologische Physik
AKB 200: Poster Session II
AKB 200.22: Poster
Dienstag, 8. März 2005, 17:00–19:00, Poster TU C
Tension-induced titin kinase activation studied by force-probe molecular dynamics simulations — •Frauke Gräter1, Jianhua Shen2, Hualiang Jiang2, and Helmut Grubmüller1 — 1MPI fuer Biophysikalische Chemie, Am Fassberg 11, 37077 Goettingen — 2Shanghai Insitute of Materia Medica, Zuchongzhi Lu 555, Zhangjiang Hi-Tech Park, 201203 Shanghai, China
The conversion of mechanical stress into a biochemical signal in a muscle cell requires a force sensor. Titin kinase, the catalytic domain of the muscle protein titin, has been suggested as a candidate. Its activation requires major conformational changes resulting in the exposure of its active site.
Force probe molecular dynamics simulations were used to obtain insight into the tension-induced activation mechanism. Our results suggest the rupture of two terminal beta-sheets as the primary unfolding steps. The low force resistance of the C-terminal relative to the N-terminal beta-sheet is found to be due to their different topology. A subsequent movement of the auto-inhibitory tail is seen to lead to the exposure of the active site, as is required for titin kinase activity. Thus, our reults support the hypothesis of titin kinase as a force sensor.