4H1W

E1 structure of the (SR) Ca2+-ATPase in complex with Sarcolipin

4H1W の概要

• エントリーDOI: 10.2210/pdb4h1w/pdb
• 関連するPDBエントリー: 1T5S 1T5T 2C8K 3B9B
• 分子名称: SERCA1a, Sarcolipin, POTASSIUM ION, ... (6 entities in total)
• 機能のキーワード: p-type atpase, ca2+ transport, sarcolipin, phospholamban, membrane protein, hydrolase-hydrolase regulator complex, hydrolase/hydrolase regulator
• 由来する生物種: Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits); 詳細
• 細胞内の位置: Membrane ; Multi-pass membrane protein : B6CAM1; Sarcoplasmic reticulum membrane ; Single-pass membrane protein : P42532
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 113996.34

構造登録者

Bublitz, M.,Winther, A.-M.L.,Karlsen, J.,Moller, J.V.,Hansen, J.B.,Buch-Pedersen, M.J.,Nissen, P. (登録日: 2012-09-11, 公開日: 2013-03-06, 最終更新日: 2024-02-28)

主引用文献

Winther, A.M.,Bublitz, M.,Karlsen, J.L.,Moller, J.V.,Hansen, J.B.,Nissen, P.,Buch-Pedersen, M.J.
The sarcolipin-bound calcium pump stabilizes calcium sites exposed to the cytoplasm.
Nature, 495:265-269, 2013

PubMed Abstract: The contraction and relaxation of muscle cells is controlled by the successive rise and fall of cytosolic Ca(2+), initiated by the release of Ca(2+) from the sarcoplasmic reticulum and terminated by re-sequestration of Ca(2+) into the sarcoplasmic reticulum as the main mechanism of Ca(2+) removal. Re-sequestration requires active transport and is catalysed by the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), which has a key role in defining the contractile properties of skeletal and heart muscle tissue. The activity of SERCA is regulated by two small, homologous membrane proteins called phospholamban (PLB, also known as PLN) and sarcolipin (SLN). Detailed structural information explaining this regulatory mechanism has been lacking, and the structural features defining the pathway through which cytoplasmic Ca(2+) enters the intramembranous binding sites of SERCA have remained unknown. Here we report the crystal structure of rabbit SERCA1a (also known as ATP2A1) in complex with SLN at 3.1 Å resolution. The regulatory SLN traps the Ca(2+)-ATPase in a previously undescribed E1 state, with exposure of the Ca(2+) sites through an open cytoplasmic pathway stabilized by Mg(2+). The structure suggests a mechanism for selective Ca(2+) loading and activation of SERCA, and provides new insight into how SLN and PLB inhibition arises from stabilization of this E1 intermediate state without bound Ca(2+). These findings may prove useful in studying how autoinhibitory domains of other ion pumps modulate transport across biological membranes.

PubMed: 23455424
DOI: 10.1038/nature11900

実験手法

X-RAY DIFFRACTION (3.1 Å)