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PDBsum entry 3ba6
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References listed in PDB file
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Key reference
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Title
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The structural basis of calcium transport by the calcium pump.
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Authors
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C.Olesen,
M.Picard,
A.M.Winther,
C.Gyrup,
J.P.Morth,
C.Oxvig,
J.V.Møller,
P.Nissen.
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Ref.
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Nature, 2007,
450,
1036-1042.
[DOI no: ]
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PubMed id
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Abstract
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The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in
muscle function and metabolism. Here we present functional studies and three new
crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the
phosphoenzyme intermediates associated with Ca2+ binding, Ca2+ translocation and
dephosphorylation, that are based on complexes with a functional ATP analogue,
beryllium fluoride and aluminium fluoride, respectively. The structures complete
the cycle of nucleotide binding and cation transport of Ca2+-ATPase.
Phosphorylation of the enzyme triggers the onset of a conformational change that
leads to the opening of a luminal exit pathway defined by the transmembrane
segments M1 through M6, which represent the canonical membrane domain of P-type
pumps. Ca2+ release is promoted by translocation of the M4 helix, exposing Glu
309, Glu 771 and Asn 796 to the lumen. The mechanism explains how P-type ATPases
are able to form the steep electrochemical gradients required for key functions
in eukaryotic cells.
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Figure 1.
Figure 1: Overall comparison of SERCA1a structures representing
key states of the reaction cycle. The new structures of
Ca[2]E1  P-AMPPN,
E2-BeF[3]^- and E2-AlF[4]^- complexes form the basis of this
report and the E2-BeF[3]^- complex is increased in size to
emphasize its critical importance. Cation- and
nucleotide-exchange reactions are indicated. The structures are
depicted by grey, transparent surfaces and by cartoon
representations, with the A domain in yellow, N domain in red, P
domain in blue, transmembrane segment M1–2 in purple, M3–4
in green, M5–6 in wheat and M7–10 in grey. The TGES motif
is shown by pink space-filling, residues 309, 771 and
796 (mentioned in the text) as sticks, and bound Ca^2+ ions as
grey spheres. Here, and in the following figures, structural
representations were prepared with Pymol
(http://pymol.sourceforge.net/).
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Figure 6.
Figure 6: Schematic representation of the reaction cycle. A
schematic selection of key features of Ca^2+-ATPase function is
indicated and reveals for the E2-P state the rotation of the A
domain dragging M1–2, and the changes in the position of the P
domain and N domain, pushing M3–4 in an outward and downward
direction. See the Discussion for further detail. A domain,
yellow; N domain, red; P domain, blue; helix M1–2, purple;
M3–4, green; M5–10, wheat; Ca^2+ ions and protons, green and
grey spheres, respectively.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2007,
450,
1036-1042)
copyright 2007.
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