News

The Ryanodine receptor (calcium release channel) is the largest ion channel whose structure has been solved. It is also the largest membrane protein.

The structure was solved at 4.5Å resolution through a collaboration between three prominent labs at the Columbia Medical Center: the labs of Andew Marks (leading expert on ryanodine receptor), Wayne Hendrickson (leading expert on structural biology) and Joachim Frank’s lab (leading expert on cryo-EM). Years of efforts by X-ray crystallography have been unsuccessful, with the best crystal diffracting to 7Å.

This cryo-EM structural biology approach has recently been featured by Lee Bollinger as a key component of the Precision Medicine initiative, and the solving of the RyR structure is in fact the “poster child” for this effort.

The RyR channel is the therapeutic target for a new class of drugs called Rycals that are being developed for the treatment of heart (heart failure and sudden cardiac death), muscle (muscular dystrophy and age-related loss of muscle function), and brain disorders (PTSD, Alzheimer’s Disease, and Huntington’s). Rycals are patented by Columbia University.

— Andrew Marks and Joachim Frank

UPDATES 02/05/15:

• New commentary by Ivana Kuo and Barbara Ehrlich about the Ryanodine receptor in Nature Structural & Molecular Biology.
  
• RyR in the CUMC newsroom: “Revolution in Imaging Tech Brings Heart Failure Molecule Into View”