The calcium pump is a structure of a protein nature that is responsible for the transport of calcium through cell membranes. This structure is dependent on ATP and is considered an ATPase-like protein, also called Ca 2+ -ATPase.
Ca 2+ -ATPase is found in all cells of eukaryotic organisms and is essential for calcium homeostasis in the cell. This protein carries out primary active transport, since the movement of calcium molecules goes against their concentration gradient.
Functions of the calcium pump
Ca 2+ plays important roles in the cell, so its regulation within them is essential for its proper functioning. Often acts as a second messenger.
In extracellular spaces, the Ca 2+ concentration is approximately 10,000 times higher than within cells. An increased concentration of this ion in the cell cytoplasm triggers various responses, such as muscle contractions, release of neurotransmitters, and the breakdown of glycogen.
There are several ways of transferring these ions from cells: passive transport (nonspecific exit), ion channels (movement in favor of their electrochemical gradient), secondary active transport of the anti-support type (Na / Ca), and primary active transport with the pump. dependent on ATP.
Unlike the other Ca 2+ displacement mechanisms , the pump operates in vector form. That is, the ion moves in only one direction so that it only works by expelling them.
The cell is extremely sensitive to changes in Ca 2+ concentration . By presenting such a marked difference with their extracellular concentration, it is therefore so important to efficiently restore their normal cytosolic levels.
Three types of Ca 2+ -ATPases have been described in animal cells, according to their locations in the cells; pumps located in the plasma membrane (PMCA), those located in the endoplasmic reticulum and nuclear membrane (SERCA), and those found in the Golgi apparatus membrane (SPCA).
SPCA pumps also transport Mn 2+ ions that are cofactors of various enzymes in the Golgi apparatus matrix.
Yeast cells, other eukaryotic organisms and plant cells present other very particular types of Ca 2+ -ATPases.
In the plasma membrane we find the active antiportic Na / Ca transport, which is responsible for the displacement of a significant amount of Ca 2+ in cells at rest and activity. In most cells in a resting state, the PMCA pump is responsible for transporting calcium to the outside.
These proteins are made up of about 1,200 amino acids, and have 10 transmembrane segments. There are 4 main units in the cytosol . The first unit contains the terminal amino group. The second has basic characteristics, allowing it to bind to activating acid phospholipids.
In the third unit there is an aspartic acid with catalytic function, and “downstream” of this a fluorescein isotocyanate binding band, in the ATP binding domain.
In the fourth unit is the calmodulin binding domain, the recognition sites of certain kinases (A and C) and the allosteric Ca 2+ binding bands .
SERCA pumps are found in large quantities in the sarcoplasmic reticulum of muscle cells and their activity is related to contraction and relaxation in the muscle movement cycle. Its function is to transport Ca 2+ from the cytosol of the cell to the matrix of the reticulum.
These proteins consist of a single polypeptide chain with 10 transmembrane domains. Its structure is basically the same as that of PMCA proteins, but it differs in that they only have three units within the cytoplasm, the active site being in the third unit.
The functioning of this protein requires a balance of charges during the transport of ions. Two Ca 2+ (by hydrolyzed ATP) are displaced from the cytosol to the reticulum matrix, against a very high concentration gradient.
This transport occurs in an antiportal manner, since at the same time two H + are directed to the cytosol from the matrix.
Mechanism of operation
The transport mechanism is divided into two states E1 and E2. In E1 the binding sites that have a high affinity for Ca 2+ are directed towards the cytosol. In E2, the binding sites are directed towards the lumen of the reticulum, presenting a low affinity for Ca 2+ . The two Ca 2+ ions bond after transfer.
During the binding and transfer of Ca 2+ , conformational changes occur, including the opening of the M domain of the protein, which is towards the cytosol. The ions then bind more easily to the two binding sites of said domain.
The union of the two Ca 2+ ions promotes a series of structural changes in the protein. Among them the rotation of certain domains (domain A) that reorganizes the units of the pump, enabling the opening towards the reticulum matrix to release the ions, which are uncoupled thanks to the decrease in the affinity at the binding sites.
The H + protons and the water molecules stabilize the Ca 2+ binding site , causing the A domain to rotate back to its original state, closing access to the endoplasmic reticulum.
This type of pump is found in all eukaryotic cells and is responsible for the expulsion of Ca 2+ towards the extracellular space in order to keep its concentration stable within the cells.
In this protein, a Ca 2+ ion is transported by hydrolyzed ATP. Transport is regulated by the levels of the calmodulin protein in the cytoplasm.
By increasing the concentration of cytosolic Ca 2+ , calmodulin levels increase, which bind to calcium ions. The Ca 2+ -calmodulin complex then assembles to the binding site of the PMCA pump. A conformational change occurs in the pump that allows the opening to be exposed to the extracellular space.
Calcium ions are released, restoring normal levels inside the cell. Consequently the Ca 2+ -calmodulin complex disassembles, returning the conformation of the pump to its original state.
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