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Three-dimensional cryo-electron microscopy of the calcium ion pump in the sarcoplasmic reticulum membrane

An Erratum to this article was published on 20 May 1993


THE ATP-driven calcium pump (Ca2+-ATPase) is an integral membrane protein (Mr 11 OK) which relaxes striated muscle by pumping calcium out of the cytoplasm into the sarcoplasmic reticulum against a large concentration gradient1. Recent efforts have attempted to relate the sequence of Ca2+-ATPase to its structure and function. In particular, site-directed mutagenesis has identified critical amino-acid residues2–6, and its predicted secondary structure, which includes ten transmembrane helices7, has gained experimental support8–10. But direct visualization of the molecule has so far been limited to the cytoplasmic domains at low resolution11, 12. We present here the three-dimensional structure of Ca2+-ATPase in the native sarcoplasmic reticulum membrane at 14 Å resolution, determined by cryo-electron microscopy and helical image analysis. The structure shows an unexpected transmembrane organization, consisting of three distinct segments, one of which is highly inclined. These features can be related to earlier predictions of secondary structure.

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Toyoshima, C., Sasabe, H. & Stokes, D. Three-dimensional cryo-electron microscopy of the calcium ion pump in the sarcoplasmic reticulum membrane. Nature 362, 469–471 (1993).

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