Defense Date


Document Type


Degree Name

Master of Science


Physiology and Biophysics

First Advisor

Montserrat Samso

Second Advisor

Jose Miguel Eltit

Third Advisor

John Bigbee


The RyR1 acts as an intracellular calcium channel that allows passage of Ca2+ from the sarcoplasmic reticulum to the cytoplasm; this increase in cytosolic Ca2+ is required for excitation-contraction coupling. Certain mutations in RyR1 have been directly linked to malignant hyperthermia (MH) and central core disease. In a series of studies, the role of Mg2+ has been explored as it pertains to MH, and it has been determined that dysregulation of Mg2+ can even lead to MH in patients without mutations. Consequently, the aim of the study was to insert the RyR1 into nanodiscs, small, circular lipid bilayers used to solubilize membrane proteins, and to use cryo-electron microscopy to assess the conformation of the RyR1 in the presence of Mg2+ and AMP-PCP. Particle reconstruction generated a 9.0 Å resolution map that confirmed successful incorporation of the RyR1 into nanodiscs and allowed visualization of the RyR1 in a physiological closed state.


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Available for download on Wednesday, August 03, 2022