Structural dynamics of troponin during activation of skeletal muscle

TY - JOUR

T1 - Structural dynamics of troponin during activation of skeletal muscle

AU - Fusi, Luca

AU - Brunello, Elisabetta

AU - Sevrieva, Ivanka R

AU - Sun, Yin-Biao

AU - Irving, Malcolm

PY - 2014/3/25

Y1 - 2014/3/25

N2 - Time-resolved changes in the conformation of troponin in the thin filaments of skeletal muscle were followed during activation in situ by photolysis of caged calcium using bifunctional fluorescent probes in the regulatory and the coiled-coil (IT arm) domains of troponin. Three sequential steps in the activation mechanism were identified. The fastest step (1,100 s(-1)) matches the rate of Ca(2+) binding to the regulatory domain but also dominates the motion of the IT arm. The second step (120 s(-1)) coincides with the azimuthal motion of tropomyosin around the thin filament. The third step (15 s(-1)) was shown by three independent approaches to track myosin head binding to the thin filament, but is absent in the regulatory head. The results lead to a four-state structural kinetic model that describes the molecular mechanism of muscle activation in the thin filament-myosin head complex under physiological conditions.

AB - Time-resolved changes in the conformation of troponin in the thin filaments of skeletal muscle were followed during activation in situ by photolysis of caged calcium using bifunctional fluorescent probes in the regulatory and the coiled-coil (IT arm) domains of troponin. Three sequential steps in the activation mechanism were identified. The fastest step (1,100 s(-1)) matches the rate of Ca(2+) binding to the regulatory domain but also dominates the motion of the IT arm. The second step (120 s(-1)) coincides with the azimuthal motion of tropomyosin around the thin filament. The third step (15 s(-1)) was shown by three independent approaches to track myosin head binding to the thin filament, but is absent in the regulatory head. The results lead to a four-state structural kinetic model that describes the molecular mechanism of muscle activation in the thin filament-myosin head complex under physiological conditions.

U2 - 10.1073/pnas.1321868111

DO - 10.1073/pnas.1321868111

M3 - Article

C2 - 24616505

SN - 0027-8424

VL - 111

SP - 4626

EP - 4631

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 12

ER -