Sandbox Reserved 970: Difference between revisions

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The calcium ATPase is a protein composed of 1001 aminoacids.

The protein is ~~composed of many~~ <scene name='60/604489/Alpha_regions/1'>alpha helices regions</scene>~~, including~~ 10 transmembrane alpha helices. ~~It also contains~~ a ~~lot~~ of ~~beta strands~~.

The protein is very rich in <scene name='60/604489/Alpha_regions/1'>alpha helices regions</scene>. It contains 10 transmembrane alpha helices, and three of them line a channel that spans the lipid bilayer and that allows calcium to pass through membranes. When the protein isn’t phosphorylated, two of the transmembrane helices are disrupted and form a cavity that can bind two molecules of calcium.

The calcium pump is organized in four major domains:

- The transmembrane portion of the protein contains the channel that span the lipid bilayer, and the calcium binding cavity.

- The nucleotide binding domain, where ATP binds to the protein.

- The phosphorylation domain contains an Aspartate residue (Asp 351) that can be phosphorylated.

- The activator domain.

== Ligand and Interaction ==

The architecture of calcium ATPase (determined by X-Ray crystallography) allow to understand mechanisms by which the energy of ATP is coupled to the calcium transport across a membrane.

~~Structurally~~, the ~~pump contains 10~~ transmembrane ~~domains (α~~ helices), two ~~large intracellular loops~~ and ~~amino/carboxy-terminal cytoplasmic tails~~.

'''The first step of the calcium pump catalytic cycle is the cooperative binding of two calcium ions in the calcium binding cavity. Then, ATP binds to the ATP binding site (nucleotide binding domain) and transfers its γ-phosphate to the aspartic acide 351 (phosphorylation domain). That creates a acid-stable aspartyl phosphate intermediate. The phosphorylation of Asp351 allows a large conformational changes in cytoplasmic domains: the nucleotide binding domain and the phosphorylation domain are brought into close proximity. This rearrangement causes a 90° rotation of the activator domain, which leads to a rearrangement of the transmembrane helices. This rearrangement alters the affinity of the protein for the calcium and disrupts the calcium binding cavity. Calcium is released in the lumen of the endoplasmic reticulum/Golgi Apparatus or outside the cell. After releasing calcium, two protons are bound to the transport sites (charges compensation) and the aspartyl phosphate is hydrolyzed to complete the cycle.'''

In the cytoplasm, the ATP binds to the cytosolic loop that connects transmembrane domains four and five (ATP binding site). It transfers its γ-phosphate to the aspartic acide 351 (phosphorylation site) and creates a acid-stable aspartyl phosphate intermediate. The binding of ATP is initiated by the cooperative fixing of two calcium ions to the transport site. The phosphorylation of Asp351 allows a large conformational changes in cytoplasmic domains which closes the ion gates from the cytoplasm and alters the affinity of the protein for the calcium. After releasing calcium (in the lumen of cytoplasm or out side the cell), two protons are bound to the transport sites (charges compensation) and the aspartyl phosphate is hydrolyzed to complete the cycle.

To sum up, calcium pumps have two conformations, E1 and E2. E1 has the calcium binding site oriented toward the cytoplasm . E2 has the calcium binding site oriented toward the lumen of the endoplasmic reticulum or toward the extracellular background. These two conformations are characterized by different specificity for ion binding.

== Biological Function and Localisation ==

The pumps exist in two major conformational states : E1 and E2. When the pump is in the E1 state, it has high calcium affinity and interacts with calcium at one side of the membrane. In the E2 state, the enzyme has a lower calcium affinity and that leads to the release of the ion at the opposite side.

Recently, some structural work on the SERCA pump has shown that the mechanism of the pump is a little bit more complex. When the calcium pump is unphosphorylated, two of the helices are disrupted, forming a cavity accessible from the cytosol. This cavity binds two calcium ions. When ATP binds to the pump, it allows the phosphorylation of the enzyme on its phosphorylation domain. The hydrolysis of ATP causes conformational changes that bring the nucleotide binding domain and the phosphorylation domain of the enzyme into close proximity. The activator domain rotates and the transmembrane helices 4 and 6 rearrange. Calcium is released into the lumen of the sarcoplasmic reticulum.

More recent structural work on the SERCA pump has increased the complexity of the conformational transitions that occur during the catalytic cycle. Upon binding of Ca2+, a series of structural changes occur that involve both the protruding cytoplasmic sector and the transmembrane domains, permitting the phosphorylation of the catalytic D-residue by the γ-phosphate of ATP. The dissociation of Ca2+ from the enzyme follows the transition of the high Ca2+ affinity E1∼P(Ca2+) enzyme to the lower affinity E2-P enzyme, the hydrolysis of which then regenerates the Ca2+-free E2 ATPase, completing the catalytic cycle.

== Regulations ==

Sandbox Reserved 970: Difference between revisions

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@@ Line 9: / Line 9: @@
 The calcium ATPase is a protein composed of 1001 aminoacids.
-The protein is composed of many <scene name='60/604489/Alpha_regions/1'>alpha helices regions</scene>, including 10 transmembrane alpha helices. It also contains a lot of beta strands.
+The protein is very rich in <scene name='60/604489/Alpha_regions/1'>alpha helices regions</scene>. It contains 10 transmembrane alpha helices, and three of them line a channel that spans the lipid bilayer and that allows calcium to pass through membranes. When the protein isn’t phosphorylated, two of the transmembrane helices are disrupted and form a cavity that can bind two molecules of calcium.
+The calcium pump is organized in four major domains:
+-	The transmembrane portion of the protein contains the channel that span the lipid bilayer, and the calcium binding cavity.
+-	The nucleotide binding domain, where ATP binds to the protein.
+-	The phosphorylation domain contains an Aspartate residue (Asp 351) that can be phosphorylated.
+-	The activator domain.
 == Ligand and Interaction ==
 The architecture of calcium ATPase (determined by X-Ray crystallography) allow to understand mechanisms by which the energy of ATP is coupled to the calcium transport across a membrane.
-Structurally, the pump contains 10 transmembrane domains (α helices), two large intracellular loops and amino/carboxy-terminal cytoplasmic tails.
+'''The first step of the calcium pump catalytic cycle is the cooperative binding of two calcium ions in the calcium binding cavity. Then, ATP binds to the ATP binding site (nucleotide binding domain) and transfers its γ-phosphate to the aspartic acide 351 (phosphorylation domain). That creates a acid-stable aspartyl phosphate intermediate. The phosphorylation of Asp351 allows a large conformational changes in cytoplasmic domains: the nucleotide binding domain and the phosphorylation domain are brought into close proximity. This rearrangement causes a 90° rotation of the activator domain, which leads to a rearrangement of the transmembrane helices. This rearrangement alters the affinity of the protein for the calcium and disrupts the calcium binding cavity. Calcium is released in the lumen of the endoplasmic reticulum/Golgi Apparatus or outside the cell. After releasing calcium, two protons are bound to the transport sites (charges compensation) and the aspartyl phosphate is hydrolyzed to complete the cycle.'''
 In the cytoplasm, the ATP binds to the cytosolic loop that connects transmembrane domains four and five (ATP binding site). It transfers its γ-phosphate to the aspartic acide 351 (phosphorylation site) and creates a acid-stable aspartyl phosphate intermediate. The binding of ATP is initiated by the cooperative fixing of two calcium ions to the transport site. The phosphorylation of Asp351 allows a large conformational changes in cytoplasmic domains which closes the ion gates from the cytoplasm and alters the affinity of the protein for the calcium. After releasing calcium (in the lumen of cytoplasm or out side the cell), two protons are bound to the transport sites (charges compensation) and the aspartyl phosphate is hydrolyzed to complete the cycle.
 To sum up, calcium pumps have two conformations, E1 and E2. E1 has the calcium binding site oriented toward the cytoplasm . E2 has the calcium binding site oriented toward the lumen of the endoplasmic reticulum or toward the extracellular background. These two conformations are characterized by different specificity for ion binding.
 == Biological Function and Localisation ==
-The pumps exist in two major conformational states : E1 and E2. When the pump is in the E1 state, it has high calcium affinity and interacts with calcium at one side of the membrane. In the E2 state, the enzyme has a lower calcium affinity and that leads to the release of the ion at the opposite side.
-Recently, some structural work on the SERCA pump has shown that the mechanism of the pump is a little bit more complex. When the calcium pump is unphosphorylated, two of the helices are disrupted, forming a cavity accessible from the cytosol. This cavity binds two calcium ions. When ATP binds to the pump, it allows the phosphorylation of the enzyme on its phosphorylation domain. The hydrolysis of ATP causes conformational changes that bring the nucleotide binding domain and the phosphorylation domain of the enzyme into close proximity. The activator domain rotates and the transmembrane helices 4 and 6 rearrange. Calcium is released into the lumen of the sarcoplasmic reticulum.
-More recent structural work on the SERCA pump has increased the complexity of the conformational transitions that occur during the catalytic cycle. Upon binding of Ca2+, a series of structural changes occur that involve both the protruding cytoplasmic sector and the transmembrane domains, permitting the phosphorylation of the catalytic D-residue by the γ-phosphate of ATP. The dissociation of Ca2+ from the enzyme follows the transition of the high Ca2+ affinity E1∼P(Ca2+) enzyme to the lower affinity E2-P enzyme, the hydrolysis of which then regenerates the Ca2+-free E2 ATPase, completing the catalytic cycle.
 == Regulations ==