National Center for Macromolecular Imaging
Calcium Release Channel
Susan L. Hamilton, Irina I. Serysheva, Steve J. Ludtke and Wah Chiu


Using a combination of bioinformatics, electron cryomicroscopy and biochemical techniques, we have identified an oxidoreductase-like domain in the skeletal muscle Ca2+ release channel protein (RYR1). The initial prediction was derived from sequence-based fold recognition for the N-terminal region (41-420) of RYR1. The putative domain was computationally localized to the clamp domain in the cytoplasmic region of a 22Å structure of RYR1. This localization was subsequently confirmed by difference imaging with a sequence specific antibody. Consistent with the prediction of an oxidoreductase domain, RYR1 binds [3H]NAD+, supporting a model in which RYR1 has an oxidoreductase domain.

Selected Images


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The open(left) and closed(right) state are shown in three different views: top, side and buttom. Important details are marked: the clamp-shaped domain to the central part of the cytoplasmic side ("CY") of the tetramer. The putative transmembrane ("TM") part of the assembly resembles the stem of the mushroom-shaped protein. In the open-state reconstruction the transmembrane region of the channel appears open towards the SR, whereas in the closed state a central opening is not seen in this region. As is clearly visible in these images, the clamp-shaped domains ("C") are open in the open-state reconstruction whereas the fingers of the clamps touch in the closed state reconstruction. The open(left) and closed(right) state are shown in three different views: top, side and buttom. Important details are marked: the clamp-shaped domain to the central part of the cytoplasmic side ("CY") of the tetramer. The putative transmembrane ("TM") part of the assembly resembles the stem of the mushroom-shaped protein. In the open-state reconstruction the transmembrane region of the channel appears open towards the SR, whereas in the closed state a central opening is not seen in this region. As is clearly visible in these images, the clamp-shaped domains ("C") are open in the open-state reconstruction whereas the fingers of the clamps touch in the closed state reconstruction.

Selected Publications

 
  • Baker, M. L., Serysheva, I. I., Sencer, S., Wu, Y., Ludtke, S. J., Jiang, W., Hamilton, S. L. & Chiu, W. (2002). The skeletal muscle Ca2+ release channel has an oxidoreductase-like domain. Proc Natl Acad Sci U S A 99: 12155-12160.

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  • Serysheva, I.I., Schatz, M., van Heel, M., Chiu, W. and Hamilton, S.L. (1999). Structure of the skeletal muscle calcium release channel activated with Ca2+ and AMP-PCP. Biophys. J. 77:1936-1944.

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  • Orlova, E.V., Serysheva, I.I., van Heel, M., Hamilton, S.L. and Chiu, W. (1996). Two structural configurations of the skeletal muscle calcium release channel. Nature Structural Biology. 3:547-552.