1. Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan
2. Present address: Department of Immunology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan

Correspondence to: Chikashi Toyoshima Email: ct@iam.u-tokyo.ac.jp
The atomic coordinates are deposited in the PDB under accession code 1VFP.

Abstract

P-type ATPases are ATP-powered ion pumps that establish ion concentration gradients across cell and organelle membranes. Here, we describe the crystal structure of the Ca²⁺ pump of skeletal muscle sarcoplasmic reticulum, a representative member of the P-type ATPase superfamily, with an ATP analogue, a Mg²⁺ and two Ca²⁺ ions in the respective binding sites. In this state, the ATP analogue reorganizes the three cytoplasmic domains (A, N and P), which are widely separated without nucleotide, by directly bridging the N and P domains. The structure of the P-domain itself is altered by the binding of the ATP analogue and Mg²⁺. As a result, the A-domain is tilted so that one of the transmembrane helices moves to lock the cytoplasmic gate of the transmembrane Ca²⁺-binding sites. This appears to be the mechanism for occluding the bound Ca²⁺ ions, before releasing them into the lumen of the sarcoplasmic reticulum.

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