User:Madison Summers/Sandbox 1

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Mitochondrial Calcium Uniporter, E. coli

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1 Introduction
- 1.1 selectivity pore
2 Disease
3 Relevance
4 Structural highlights and mechanism
- 4.1 Transmembrane Domain
- 4.2 Soluble Domain

Introduction

selectivity pore

Disease

Relevance

Calcium signaling

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 Calcium, near the surface of the inner mitochondrial membrane. Activity of the uniporter is dependent on membrane potential and calcium concentration. Calcium from the cytoplasm enters the mitochondrial innermemnrane space through the mitochondrial membrane and is passed to the mitochondrial matrix via the MCU.

Figure 2: structure of mitochondrial calcium uniporter

Transmembrane Domain

The is on the inner mitochondrial membrane open to the inner membrane space. The small pore, highly specific for calcium binding is located in (TM2) while (TM1) surrounds the pore. The transmembrane domain exhibits four fold rotational symmetry. The domain swapping of TM1 of one subunit with the TM2 of the neighboring subunits allows for a tight packing in the transmembrane connectivity. 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 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. The wider opening allows calcium to rehydrate once they pass the selectivity pore. Connectivity between subunits provide flexibility of the uniporter.

Soluble Domain

The is the first subsection of the soluble domain, which resides in the inner mitochondrial membrane. The coiled coil functions as the joints of the uniporter, providing flexibility to promote transport of Calcium ions down their concentration gradient. The junction between the transmembrane domain and the coiled coil's flexibility can be attributed to the disordered packing between subunits; subunits A and C adopt different conformations than the B and D subunits, although they superimpose well. When calcium binds to the selectivity pore, the coiled coil swings approximately 8 degrees around its end near the . This movement propagates to the top of the transmembrane domain, where the pore is located, about 85 amperes away. The largest displacement triggered by the movement of the coiled coil is in the transmembrane domain, where the coil bends 20 degrees, moving the transmembrane domain further apart.

References

^[1] ^[2]

↑ 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:http://dx.doi.org/10.1002/1873-3468.12677
↑ Yoo J, Wu M, Yin Y, Herzik MA Jr, Lander GC, Lee SY. Cryo-EM structure of a mitochondrial calcium uniporter. Science. 2018 Jun 28. pii: science.aar4056. doi: 10.1126/science.aar4056. PMID:29954988 doi:http://dx.doi.org/10.1126/science.aar4056

Student Contributors

Madison Summers
Holly Rowe
Lizzy Ratz

Proteopedia Page Contributors and Editors (what is this?)

Madison Summers

Retrieved from "http://52.214.119.220/wiki/index.php/User:Madison_Summers/Sandbox_1"

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 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. The domain swapping of TM1 of one subunit with the TM2 of the neighboring subunits allows for a tight packing in the transmembrane connectivity.  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 <scene name='83/837230/Charge/2'>glutamates carboxyl group </scene> 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. The wider opening allows calcium to rehydrate once they pass the selectivity pore. Connectivity between subunits provide flexibility of the uniporter.
 ===Soluble Domain===
-The <scene name='83/837230/Coiled_coil/3'>coiled coil</scene> is the first subsection of the soluble domain, which resides in the inner mitochondrial membrane. The coiled coil functions as the joints of the uniporter, providing flexibility to promote transport of Calcium ions down their concentration gradient. When calcium binds to the selectivity pore, the coiled coil swings approximately 8 degrees around its end near the <scene name='83/837230/Coiled_coil/3'>N-terminal domain</scene>. This movement propagates to the top of the transmembrane domain, where the pore is located, about 85 amperes away. The largest displacement triggered by the movement of the coiled coil is in the transmembrane domain, where the coil bends 20 degrees, moving the transmembrane domain further apart.
+The <scene name='83/837230/Coiled_coil/3'>coiled coil</scene> is the first subsection of the soluble domain, which resides in the inner mitochondrial membrane. The coiled coil functions as the joints of the uniporter, providing flexibility to promote transport of Calcium ions down their concentration gradient. The junction between the transmembrane domain and the coiled coil's flexibility can be attributed to the disordered packing between subunits; subunits A and C adopt different conformations than the B and D subunits, although they superimpose well. When calcium binds to the selectivity pore, the coiled coil swings approximately 8 degrees around its end near the <scene name='83/837230/Coiled_coil/3'>N-terminal domain</scene>. This movement propagates to the top of the transmembrane domain, where the pore is located, about 85 amperes away. The largest displacement triggered by the movement of the coiled coil is in the transmembrane domain, where the coil bends 20 degrees, moving the transmembrane domain further apart.