Cytochrome C -Adis: Difference between revisions
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==Cytochrome '' | ==Cytochrome ''C''== | ||
<StructureSection load='3CP5' size='340' side='right' caption='Cytochrome C with a heme complex' scene=''> | <StructureSection load='3CP5' size='340' side='right' caption='Cytochrome C with a heme complex' scene=''> | ||
Cytochrome | Cytochrome ''C'' is a [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins] family protein due to its alpha helical core that is normally located within the space between the inner mitochondrial membrane and outer mitochondrial membrane. It is a vital part of the respiratory cycle taking a key role in the transfer of electrons from complex III to complex IV. Cytochrome ''C'' is also one of the initiation proteins for apoptosis or cell death. One method of apoptosis is completely reliant on the release of Cytochrome ''C'' into the cytosol in order to initiate apoptosis. Different attachments to the central heme group of Cytochrome ''C'' cause it to have different functions overall. The protein structure and function differ, but it is still considered to be a Cytochrome C protein. The composition of Cytochrome ''C'' is relatively quite simple in comparison to other major proteins since approximately 20% of its residues being Lysine (The Journal of Biochemistry). Cytochrome ''C'', since it is so small, it has been the subject of many experiments. The structure being easy to map out and capable of being edited makes it a popular protein to experiment with even though it has the heme group causing some issues and complexity. However simple, it is a crucial protein for overall function in all Eukaryotes.(New Journal of Science). It is also an ancient protein that was established in the earliest stages of life but was not discovered until 1886 by Charles A. Macmunn. Cytochrome ''C'' was also rediscovered in 1925 by Charles Keilin. Since then, many have experimented with the inhibition of cytochrome ''C'' release which has shown promising results in therapeutic potential for Huntington’s disease. Others have used Cytochrome ''C'' in cancer research using it for its apoptosis function. The relatively small protein has a diverse job description causing it to be one of the most versatile experimental proteins known to this day. | ||
== Structure == | == Structure == | ||
Cytochrome 'C' is a [http://en.wikipedia.org/wiki/Heme heme] protein (or a part of the heme family) which means that it has a | Cytochrome ''C'' is a [http://en.wikipedia.org/wiki/Heme heme] protein (or a part of the heme family) which means that it has a | ||
heme prosthetic group. This <scene name='Sandbox_Reserved_335/Axial/6'>heme prosthetic</scene> group is covalently bonded using thioether bonds to Histidine and Methionine residues. This heme prosthetic is four cyclic structures forming a macrocycle which coordinates functionality about a central | heme prosthetic group. This <scene name='Sandbox_Reserved_335/Axial/6'>heme prosthetic</scene> group is covalently bonded using thioether bonds to Histidine and Methionine residues. This heme prosthetic is four cyclic structures forming a macrocycle which coordinates functionality about a central | ||
iron atom. They can form different compounds by having different attachments around the 4 | iron atom. They can form different compounds by having different attachments around the 4 | ||
pyrrole rings. Two unique structures of Cytochrome 'C' exist naturally but both having the same general motif or <scene name='Sandbox_Reserved_335/Motif/1'>basic structure</scene>. In the monoheme | pyrrole rings. Two unique structures of Cytochrome ''C'' exist naturally but both having the same general motif or <scene name='Sandbox_Reserved_335/Motif/1'>basic structure</scene>. In the monoheme | ||
form, the other axial position is usually left empty however, it can be occupied by other | form, the other axial position is usually left empty however, it can be occupied by other | ||
molecules such as histidine or lysine. Leaving the location empty prevents steric hindrance and | molecules such as histidine or lysine. Leaving the location empty prevents steric hindrance and | ||
allows for easier attachment. The other forms contain anywhere from one to four methionine | allows for easier attachment. The other forms contain anywhere from one to four methionine | ||
groups on the occupied side of the heme group. When drawn out, the structure of | groups on the occupied side of the heme group. When drawn out, the structure of | ||
Cytochrome 'C' looks vertically and horizontally symmetrical due to the central heme group prior | Cytochrome ''C'' looks vertically and horizontally symmetrical due to the central heme group prior | ||
to adding side chains. The side chains which determine overall function are branched off of the | to adding side chains. The side chains which determine overall function are branched off of the | ||
central heme group and vary depending on the proteins location in the cell. They can have one | central heme group and vary depending on the proteins location in the cell. They can have one | ||
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== Function == | == Function == | ||
Cytochrome 'C' function is dependent on the conformation of the structure it is portraying | Cytochrome ''C'' function is dependent on the conformation of the structure it is portraying | ||
at the time which is primarily determined by the location of the Cytochrome 'C' protein within the | at the time which is primarily determined by the location of the Cytochrome ''C'' protein within the | ||
cell. Monoheme Cytochrome 'C', which is primarily found in the mitochondria of the cell, | cell. Monoheme Cytochrome ''C'', which is primarily found in the mitochondria of the cell, | ||
functions in eukaryotes the electron transport chain. Cytochrome 'C' is an electron | functions in eukaryotes the electron transport chain. Cytochrome ''C'' is an electron | ||
transfer protein during the bc1 complex of the electron transport chain. (See below for more | transfer protein during the bc1 complex of the electron transport chain. (See below for more | ||
detailed information) Involving identical structure to the Cytochrome 'C' protein in <scene name='81/814739/Bc1_complex_cytc/1'>mitochondria</scene>, | detailed information) Involving identical structure to the Cytochrome ''C'' protein in <scene name='81/814739/Bc1_complex_cytc/1'>mitochondria</scene>, | ||
one conformation of Cytochrome 'C' is also a member of the electron transport chain in | one conformation of Cytochrome ''C'' is also a member of the electron transport chain in | ||
photosynthesis in plants. (PDB101: Molecule of the Month: Cytochrome c.) | photosynthesis in plants. (PDB101: Molecule of the Month: Cytochrome c.) | ||
Cytochrome 'C' is also a main signaling factor for | Cytochrome ''C'' is also a main signaling factor for | ||
apoptosis of cells. In the intrinsic pathway of apoptosis, Cytochrome 'C' plays a key role in the | apoptosis of cells. In the intrinsic pathway of apoptosis, Cytochrome ''C'' plays a key role in the | ||
initiation of cell death. Without Cytochrome 'C', the cell could not release the protein into the | initiation of cell death. Without Cytochrome ''C'', the cell could not release the protein into the | ||
cytosol which at high volumes leads to intrinsic apoptosis. (see below for more detailed | cytosol which at high volumes leads to intrinsic apoptosis. (see below for more detailed | ||
information on this function) | information on this function) | ||
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to perform apoptosis. During the extrinsic pathway, an immune response is initiated by killer | to perform apoptosis. During the extrinsic pathway, an immune response is initiated by killer | ||
lymphocytes which cause an apoptotic cascade. (Apoptosis: a Review of Programmed Cell | lymphocytes which cause an apoptotic cascade. (Apoptosis: a Review of Programmed Cell | ||
Death) Cytochrome 'C' takes play in the intrinsic pathway. This is when a stimulus causes | Death) Cytochrome ''C'' takes play in the intrinsic pathway. This is when a stimulus causes | ||
Cytochrome 'C' to be released into the Cytosol. Once cytochrome 'C' is in the cytosol, it is recognized and bound to apoptotic factors which are then activated forming the apoptosome complex. Then caspases join in and are activated which result in a caspase cascade forcing | Cytochrome ''C'' to be released into the Cytosol. Once cytochrome ''C'' is in the cytosol, it is recognized and bound to apoptotic factors which are then activated forming the apoptosome complex. Then caspases join in and are activated which result in a caspase cascade forcing | ||
apoptosis. (Cytochrome c: Functions beyond Respiration.) Also over time while a cell is getting | apoptosis. (Cytochrome c: Functions beyond Respiration.) Also over time while a cell is getting | ||
old, it has degradation of its membranes. This degradation also leads to the release of | old, it has degradation of its membranes. This degradation also leads to the release of | ||
Cytochrome 'C' which would signal that the cell is old and ready to be killed off. Without | Cytochrome ''C'' which would signal that the cell is old and ready to be killed off. Without | ||
Cytochrome 'C', intrinsic apoptosis would not be possible because the apoptotic factors would | Cytochrome ''C'', intrinsic apoptosis would not be possible because the apoptotic factors would | ||
never be activated. Same as if there are mutations in Cytochrome 'C' causing it to be unable to | never be activated. Same as if there are mutations in Cytochrome ''C'' causing it to be unable to | ||
permeate through the membrane, or if there is a mutation that increases the permeability of it | permeate through the membrane, or if there is a mutation that increases the permeability of it | ||
through the membrane, the apoptotic pathway would be accelerated or inhibited. (Cytochrome C | through the membrane, the apoptotic pathway would be accelerated or inhibited. (Cytochrome C | ||
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== Purpose in ETC and Photosynthesis == | == Purpose in ETC and Photosynthesis == | ||
Cytochrome 'C' also plays a key role in the Electron Transport Chain in mitochondria. It is one of | Cytochrome ''C'' also plays a key role in the Electron Transport Chain in mitochondria. It is one of | ||
the many electron carriers in the electron transport chain but quite a vital one. The heme group | the many electron carriers in the electron transport chain but quite a vital one. The heme group | ||
portion of Cytochrome 'C' accepts the electrons from the bc1 complex and then carries the | portion of Cytochrome ''C'' accepts the electrons from the bc1 complex and then carries the | ||
electrons to complex IV. Once at complex IV, the Cytochrome 'C' release their electron that they | electrons to complex IV. Once at complex IV, the Cytochrome ''C'' release their electron that they | ||
are carrying and it is given to the Cytochrome 'C' Oxidase enzyme. This enzyme accumulates 4 | are carrying and it is given to the Cytochrome ''C'' Oxidase enzyme. This enzyme accumulates 4 | ||
electrons and transfers them to one dioxygen | electrons and transfers them to one dioxygen | ||
molecule in order to make two molecules of water. It is also found within the thylakoid | molecule in order to make two molecules of water. It is also found within the thylakoid | ||
membrane in the chloroplast of plants and green algae. In photosynthesis, | membrane in the chloroplast of plants and green algae. In photosynthesis, | ||
Cytochrome 'C' is one of the steps that transfers electrons from photosystem II to photosystem I. | Cytochrome ''C'' is one of the steps that transfers electrons from photosystem II to photosystem I. | ||
Later in the cycle, the electrochemical gradient will | Later in the cycle, the electrochemical gradient will | ||
then be used in order to synthesize ATP from ADP. (The Multiple Functions of Cytochrome c) | then be used in order to synthesize ATP from ADP. (The Multiple Functions of Cytochrome c) | ||
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== Medical/Research Purposes == | == Medical/Research Purposes == | ||
A proposal by many research scientists has been to regulate mitochondrial energy | A proposal by many research scientists has been to regulate mitochondrial energy | ||
production and ROS production through the phosphorylation of cytochrome 'C'. It has been | production and ROS production through the phosphorylation of cytochrome ''C''. It has been | ||
observed that Tyr48Glu phosphomimetic mutant Cytochrome 'C' reacts with CcO, but it is | observed that Tyr48Glu phosphomimetic mutant Cytochrome ''C'' reacts with CcO, but it is | ||
partially inhibited which leads to controlled respiration. (The Multiple Functions of Cytochrome | partially inhibited which leads to controlled respiration. (The Multiple Functions of Cytochrome | ||
c) They are proposing that “this effect plays an essential role in the prevention of ROS under | c) They are proposing that “this effect plays an essential role in the prevention of ROS under | ||
healthy conditions.” There is evidence when cellular stress is happening, Cytochrome 'C' then | healthy conditions.” There is evidence when cellular stress is happening, Cytochrome ''C'' then | ||
becomes phosphorylated. Once dephosphorylated, controlled respiration ceases which then sets | becomes phosphorylated. Once dephosphorylated, controlled respiration ceases which then sets | ||
up Cytochrome 'C' to initiate apoptosis. They report that the cellular stress causes mitochondrial | up Cytochrome ''C'' to initiate apoptosis. They report that the cellular stress causes mitochondrial | ||
membrane potential differences and it needs to be taken into account to be able to determine the | membrane potential differences and it needs to be taken into account to be able to determine the | ||
risks behind changes in OxPhos activity. The study focuses mainly on the phosphorylation of | risks behind changes in OxPhos activity. The study focuses mainly on the phosphorylation of | ||
Cytochrome 'C', but acknowledges the fact that other factors may also be affected through their | Cytochrome ''C'', but acknowledges the fact that other factors may also be affected through their | ||
actions. Others have began to focus their research on major diseases such as Huntington’s | actions. Others have began to focus their research on major diseases such as Huntington’s | ||
disease or diverse forms of cancer. In a post by the New Journal of Science, they report that the | disease or diverse forms of cancer. In a post by the New Journal of Science, they report that the | ||
closest that anyone has come to a universal cure for cancers has been with the use of the | closest that anyone has come to a universal cure for cancers has been with the use of the | ||
apoptotic function of Cytochrome 'C'. They went on to explain that tricking the body into | apoptotic function of Cytochrome ''C''. They went on to explain that tricking the body into | ||
believing these cancerous cells are ready to die, they could negate the effects of the ineffective | believing these cancerous cells are ready to die, they could negate the effects of the ineffective | ||
p53 gene. | p53 gene. | ||