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Ion Pathways in the Sarcoplasmic Reticulum Ca2+-ATPase
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Ion Pathways in the Sarcoplasmic Reticulum Ca2+-ATPase. / Bublitz, Maike; Musgaard, Maria; Poulsen, Hanne; Thøgersen, Lea; Olesen, Claus; Schiøtt, Birgit; Morth, Preben; Møller, Jesper V; Nissen, Poul.
In: Journal of Biological Chemistry, Vol. 288, 12.04.2013, p. 10759-10765.Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
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TY - JOUR
T1 - Ion Pathways in the Sarcoplasmic Reticulum Ca2+-ATPase
AU - Bublitz, Maike
AU - Musgaard, Maria
AU - Poulsen, Hanne
AU - Thøgersen, Lea
AU - Olesen, Claus
AU - Schiøtt, Birgit
AU - Morth, Preben
AU - Møller, Jesper V
AU - Nissen, Poul
PY - 2013/4/12
Y1 - 2013/4/12
N2 - The sarco(endo)plasmic reticulum Ca2+- ATPase (SERCA) is a transmembrane ion transporter belonging to the PII-type ATPases. It performs the vital task of re-sequestering cytoplasmic Ca2+ to the sarco-endoplasmic reticulum store, thereby also terminating Ca2+-induced signaling such as in muscle contraction. This article focuses on the transport pathways of Ca2+ and H+ ions across the lipid bilayer through SERCA. The ion binding sites of SERCA are accessible from either the cytoplasm or the SR/ER lumen at a time, and the Ca2+ entry and exit channels are both formed mainly by rearrangements of four N-terminal transmembrane (TM) alpha-helices. Recent improvements in the resolution of the crystal structures of rabbit SERCA1a have revealed a hydrated pathway in the Cterminal TM region leading from the ion binding sites to the cytosol. A comparison of different SERCA conformations reveals that this C-terminal pathway is exclusive to Ca2+- free E2-states, suggesting that it may play a functional role in proton release from the ion binding sites. This is in agreement with molecular dynamics (MD) simulations, mutational studies, and in striking analogy to a similar pathway recently described for the related sodium pump. We therefore suggest a model for the ion exchange mechanism in PII-ATPases including not only one, but two cytoplasmic pathways working in concert.
AB - The sarco(endo)plasmic reticulum Ca2+- ATPase (SERCA) is a transmembrane ion transporter belonging to the PII-type ATPases. It performs the vital task of re-sequestering cytoplasmic Ca2+ to the sarco-endoplasmic reticulum store, thereby also terminating Ca2+-induced signaling such as in muscle contraction. This article focuses on the transport pathways of Ca2+ and H+ ions across the lipid bilayer through SERCA. The ion binding sites of SERCA are accessible from either the cytoplasm or the SR/ER lumen at a time, and the Ca2+ entry and exit channels are both formed mainly by rearrangements of four N-terminal transmembrane (TM) alpha-helices. Recent improvements in the resolution of the crystal structures of rabbit SERCA1a have revealed a hydrated pathway in the Cterminal TM region leading from the ion binding sites to the cytosol. A comparison of different SERCA conformations reveals that this C-terminal pathway is exclusive to Ca2+- free E2-states, suggesting that it may play a functional role in proton release from the ion binding sites. This is in agreement with molecular dynamics (MD) simulations, mutational studies, and in striking analogy to a similar pathway recently described for the related sodium pump. We therefore suggest a model for the ion exchange mechanism in PII-ATPases including not only one, but two cytoplasmic pathways working in concert.
U2 - 10.1074/jbc.R112.436550
DO - 10.1074/jbc.R112.436550
M3 - Journal article
C2 - 23400778
VL - 288
SP - 10759
EP - 10765
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
ER -