Calcium is a very important signaling molecule in the body with many physiological functions including muscle contraction, neuron excitability, cell migration and growth. The mitochondria are important regulators of calcium in the body and the calcium uniporter (MCU) maintains calcium homeostasis within the mitochondria. Calcium moves in one direction from the intermembrane space through the inner mitochondrial membrane into the matrix. The matrix is more negative driven by the respiratory chain which draws calcium in and allows calcium to move down its gradient.
The MCU is a complex. Its MICU1 and MICU2 bind together and associate with EMRE which regulates MCU. The MICU1 and MICU2 act as gatekeepers. EMRE connects the MICU1 and MICU2 sensors to MCU therefore regulating calcium uptake for the protein
The selectivity pore is an integral part of the protein. This pore contains a group of glutamate with oxygen facing inward forming a carboxylate ring through which calcium enters. This negative carboxylate ring does a good job of pulling the positive calcium into the selectivity pore at the top of the protein.
Figure 1 Carboxylate ring within the selectivity pore.
[1] Cryogenic electron microscopy (Cryo-EM) was instrumental in outlining the complete structure of this protein.
Structure
Figure 2 Representation of the calcium fitting into the selectivity pore.
Function
Disease
Relevance
Structural highlights
This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
↑Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:https://dx.doi.org/10.1002/ijch.201300024
↑Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
↑Ransey E, Paredes E, Dey SK, Das SR, Heroux A, Macbeth MR. Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme EhDbr1 reveals a catalytic Zn(2+) /Mn(2+) heterobinucleation. FEBS Lett. 2017 Jul;591(13):2003-2010. doi: 10.1002/1873-3468.12677. Epub 2017, Jun 14. PMID:28504306 doi:https://dx.doi.org/10.1002/1873-3468.12677
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