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Introduction

Structure

Selectivity Filter

The selectivity filter contains Glu358, Trp354, and Pro359 to allow calcium to pass through the uniporter. The carboxylate oxygen of the Glu side chains draw in the positive calcium ion. The diameter of the carboxyl ring is 5Å, allowing only a dehydrated Ca ion to bind. Trp38, which is directly next to the Glu residues, stabilizes the carbonyl side chains through hydrogen bonding and anion pi interactions. These Trp residues also form stacking interactions with Pro359, which orientate the Glu carboxyl side chains towards the middle of the pore to interact with Ca ions.

Figure 1

Calcium Uniporter Structure

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Function

Inhibitors

Figure 2

Disease Links

Types 1 and 2 Diabetes

Pancreatic beta cells circulate insulin through the body. Glucose initiates signals allowing these cells to break down sugar and release insulin, which is all stimulated by mitochondrial energy metabolism. Calcium homeostasis plays a fundamental role in ATP production supplying energy to this process. Defects in homeostasis of calcium like chronic calcium depletion, caused by leaky Ryanodine receptors, causes types 1 and 2 diabetes through failure of this mechanism. Treatment involves targeting the MCU and MICU1 to open the calcium channel and allow more uptake of calcium ions into the mitochondria.

Heart Failure

Calcium overload in the mitochondria of cardiac cells lead to apoptotic cardiac cell death. This large amount of cell death

Relevance

Structural highlights

Student Contributors

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