User:Madison Summers/Sandbox 1: Difference between revisions
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== Structural highlights and mechanism == | == Structural highlights and mechanism == | ||
The MCU is a dimer of dimers, described as tetrameric truncated pyramid. The uniporter has only a single strong binding site located in the selectivity pore with specificity for [https://en.wikipedia.org/wiki/Calcium_signaling Calcium], near the surface of the inner mitochondrial membrane. <ref name="Fan C"> DOI: 10.1038/s41586-018-0330-9</ref> Activity of the uniporter is dependent on membrane potential and calcium concentration. Calcium from the cytoplasm enters the mitochondrial inner membrane space through the mitochondrial membrane and is passed to the mitochondrial matrix via the MCU. [[Image:structure.png|300 px|right|thumb|Figure 2: structure of mitochondrial calcium uniporter colored by functional domain designed in [http://www.pymol.org/ PyMol]. The transmembrane domain is highlighted salmon, the matrix in light cyan, coiled coil in dark violet, and the N-Terminal Domain in slate blue. [https://en.wikipedia.org/wiki/Protein_Data_Bank] [https://www.rcsb.org/structure/6DT0 6DT0] Each domain has a different functional role]] | The MCU is a <scene name='83/837230/Ntermsymmetry/1'>dimer of dimers</scene>, described as tetrameric truncated pyramid. The uniporter has only a single strong binding site located in the selectivity pore with specificity for [https://en.wikipedia.org/wiki/Calcium_signaling Calcium], near the surface of the inner mitochondrial membrane. <ref name="Fan C"> DOI: 10.1038/s41586-018-0330-9</ref> Activity of the uniporter is dependent on membrane potential and calcium concentration. Calcium from the cytoplasm enters the mitochondrial inner membrane space through the mitochondrial membrane and is passed to the mitochondrial matrix via the MCU. [[Image:structure.png|300 px|right|thumb|Figure 2: structure of mitochondrial calcium uniporter colored by functional domain designed in [http://www.pymol.org/ PyMol]. The transmembrane domain is highlighted salmon, the matrix in light cyan, coiled coil in dark violet, and the N-Terminal Domain in slate blue. [https://en.wikipedia.org/wiki/Protein_Data_Bank] [https://www.rcsb.org/structure/6DT0 6DT0] Each domain has a different functional role]] | ||
===Transmembrane Domain=== | ===Transmembrane Domain=== | ||
The <scene name='83/837230/Transmembrane_domain/3'>transmembrane domain</scene> is on the [https://en.wikipedia.org/wiki/Mitochondrion#Structure inner mitochondrial membrane] open to the inner membrane space. The small pore, highly specific for calcium binding is located in <scene name='83/837230/Tm2/1'>transmembrane 2</scene> (TM2) while <scene name='83/837230/Transmembrane_1/2'>transmembrane 1</scene> (TM1) surrounds the pore. The transmembrane domain exhibits four fold rotational symmetry. It is important that the selectivity pore is small, allowing only a dehydrated calcium molecule to interact with the 5 ampier wide glutamate ring. The negative charge of the glutamates carboxyl group attracts the positively charged Calcium ion. Approximately one helical turn below the glutamate ring of the selectivity filter, there is a tyrosine ring coming a 12 ampier wide pore allowing high conductivity. <ref name="Fan C" /> The wider opening allows calcium to rehydrate once they pass the selectivity pore. The domain swapping of TM1 of one subunit with the TM2 of the neighboring subunits allows for a tight packing in the transmembrane connectivity providing flexibility to the uniporter. | The <scene name='83/837230/Transmembrane_domain/3'>transmembrane domain</scene> is on the [https://en.wikipedia.org/wiki/Mitochondrion#Structure inner mitochondrial membrane] open to the inner membrane space. The small pore, highly specific for calcium binding is located in <scene name='83/837230/Tm2/1'>transmembrane 2</scene> (TM2) while <scene name='83/837230/Transmembrane_1/2'>transmembrane 1</scene> (TM1) surrounds the pore. The transmembrane domain exhibits four fold rotational symmetry. It is important that the selectivity pore is small, allowing only a dehydrated calcium molecule to interact with the 5 ampier wide glutamate ring. The negative charge of the glutamates carboxyl group attracts the positively charged Calcium ion. Approximately one helical turn below the glutamate ring of the selectivity filter, there is a tyrosine ring coming a 12 ampier wide pore allowing high conductivity. <ref name="Fan C" /> The wider opening allows calcium to rehydrate once they pass the selectivity pore. The domain swapping of TM1 of one subunit with the TM2 of the neighboring subunits allows for a tight packing in the transmembrane connectivity providing flexibility to the uniporter. | ||
