Sandbox Reserved 1626: Difference between revisions
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== Structure == | == Structure == | ||
The precise identity of the MCU as the major calcium transporter remained elusive until 2011. Thanks to a series of combined efforts involving NMR spectroscopy, cry-EM, and x-ray crystallography they were able to see the structure of the membrane-bound transporter and its regulatory machinery. <ref name="Woods"/> The actual MCU complex is a tetrameric dimer of dimers assembly. As show in the 3D image to the right. What the 3D image does not | The precise identity of the MCU as the major calcium transporter remained elusive until 2011. Thanks to a series of combined efforts involving NMR spectroscopy, cry-EM, and x-ray crystallography they were able to see the structure of the membrane-bound transporter and its regulatory machinery. <ref name="Woods"/> The actual MCU complex is a tetrameric dimer of dimers assembly. As show in the 3D image to the right. What the 3D image does not show is MICU1 and MICU 2, which are tight regulators of the MCU-mediated calcium uptake that actual bring in the calcium and move it towards the selectivity filter in the main MCU complex. There are three other proteins in the complete complex. EMRE, MCUb, and MCUR1. The EMRE is what associates MICU1 and MICU2 with main MCU protein. The MCUR1 has never been truly determined as to what it does for the structure but scientists are saying it helps with building of the overall structure and is non functional once the MCU becomes functional. <ref name="Giorgi" /> | ||
=== Selectivity Filter === | === Selectivity Filter === | ||
The pore-forming subunit of the MCU contains 351 amino acid residues with both the N- and C-terminal domains located in the matrix of the mitochondria. The two transmembrane domains, TM1 and TM2, are connected by a solvent- exposed loop with a highly conserved DXXE motif, which is essential for the calcium transport, located in the upper helix of TM2 | The pore-forming subunit of the MCU contains 351 amino acid residues with both the N- and C-terminal domains located in the matrix of the mitochondria. The two transmembrane domains, TM1 and TM2, are connected by a solvent- exposed loop with a highly conserved DXXE motif, which is essential for the calcium transport, located in the upper helix of TM2. The first pore-lining residues are Asp 333 and Glu336, that are both part of the highly conserved DXXE motif connecting TM1 and TM2. Each monomer has a Glu336 whose carboxylate group points toward the pore center. The diameter of the ring is 5Å meaning that the calcium is dehydrated. Trp332 stabilizes the carboxyl groups of two neighboring Glu336 residues through hydrogen bonding. The additional interaction of Trp332 with Pro337 serves to orient Glu336 for calcium coordination. Therefore, Glu336, Trp332, and Pro337 make up the highly conserved selectivity filter. <ref name="Fan"/> | ||
=== Common Mutations === | === Common Mutations === | ||
