title: Ion pathways in the sarcoplasmic reticulum Ca2+-ATPase.
abstract: The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a transmembrane ion transporter belonging to the P(II)-type ATPase family. It performs the vital task of re-sequestering cytoplasmic Ca(2+) to the sarco/endoplasmic reticulum store, thereby also terminating Ca(2+)-induced signaling such as in muscle contraction. This minireview focuses on the transport pathways of Ca(2+) and H(+) ions across the lipid bilayer through SERCA. The ion-binding sites of SERCA are accessible from either the cytoplasm or the sarco/endoplasmic reticulum lumen, and the Ca(2+) entry and exit channels are both formed mainly by rearrangements of four N-terminal transmembrane α-helices. Recent improvements in the resolution of the crystal structures of rabbit SERCA1a have revealed a hydrated pathway in the C-terminal transmembrane 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 Ca(2+)-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 simulations and mutational studies and is 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 P(II)-ATPases including not one, but two cytoplasmic pathways working in concert.
authors: Centre for Membrane Pumps in Cells and Disease (PUMPkin), Aarhus University, DK-8000 Aarhus C, Denmark.
authors: Maike
authors: M
authors: Bublitz
authors: Maria
authors: M
authors: Musgaard
authors: Hanne
authors: H
authors: Poulsen
authors: Lea
authors: L
authors: Thøgersen
authors: Claus
authors: C
authors: Olesen
authors: Birgit
authors: B
authors: Schiøtt
authors: J Preben
authors: JP
authors: Morth
authors: Jesper Vuust
authors: JV
authors: Møller
authors: Poul
authors: P
authors: Nissen
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D056004:Molecular Dynamics Simulation; D011522:Protons; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011522:Protons; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
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