Molecular mechanism of calcium signaling in muscle contraction (FWOAL766)

Our survival as living organisms depends every single second on reliable function of muscles. Functioning of our heart, breathing and even our ability to smile rely on coordinated contraction of muscles. In spite of such a central role muscle play in our everyday life molecular details of their mechanisms are still unresolved. Excitation of muscles begins with depolarization of cellular membrane initiating cascade of calcium signaling through two ion channels: voltage dependent calcium channel and calcium release channel, known as ryanodine receptor (RyR). RyR opens in response to elevated calcium concentration releasing micromolar amount of calcium from sarcoplasmic reticulum into the cytoplasm, which results in muscular contraction. The gating mechanism of RyR is unknown. To a large extend this is because the atomic structure of RyR is unknown. The objective of my proposal is to determine the atomic structure of RyR. I will use cryogenic electron microscopy (cryo-EM) to achieve this goal. Cryo-EM allows visualizing individual protein molecules imbedded in vitrified ice. Combined with sophisticated computational technique of single particle reconstruction it allows determining 3D map of the protein with atomic resolution. The determined structure will reveal the architecture of the channel and allow us to understand the series of molecular events that cause the channel to open and close in healthy cells or understand why its function is impaired in muscular diseases.

Keywords:biotechnology, muscle contraction

Disciplines:Other biotechnology, bio-engineering and biosystem engineering not elsewhere classified