The central mutation site of RyR2 was mapped to a bridge of density connecting cytoplasmic domains 5 and 6, which is distinct from the previously mapped FKBP12.6-binding site.
The study maps the central mutation site of RyR2 to a specific structural bridge, providing structural insights into mutations linked to sudden cardiac death.
The cardiac muscle ryanodine receptor (RyR2) functions as a calcium release channel in the heart. Up to 40 mutations in RyR2 have been linked to genetic forms of sudden cardiac death. These mutations are largely clustered in three regions of the sequence of the polypeptide: one near the N terminus, one in the central region, and the third in the C-terminal region. The central region includes 11 mutations, and an isoleucine-proline motif (positions 2427 and 2428) in the same region is predicted to contribute to the binding of FKBP12.6 protein. We have mapped the central mutation site in the three-dimensional structure of RyR2 by green fluorescent protein insertion, cryoelectron microscopy, and single-particle image processing. The central mutation site was mapped to a "bridge" of density that connects cytoplasmic domains 5 and 6, which have been suggested to undergo conformational changes during channel gating. Moreover, the location of this central mutation site is not close to that of the FKBP12.6-binding site mapped previously by cryoelectron microscopy.
Liu et al. (Tue,) conducted a other in Sudden cardiac death (genetic forms). Green fluorescent protein insertion and cryoelectron microscopy was evaluated on Localization of the central mutation site in the three-dimensional structure of RyR2. The central mutation site of RyR2 was mapped to a bridge of density connecting cytoplasmic domains 5 and 6, which is distinct from the previously mapped FKBP12.6-binding site.
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