Molecular simulations explain how enzymatic pumps transport calcium ions within muscle cells

Feb 18, 2011
Figure 1: Just as a breakwater can protect a shore, Glu771 can protect binding sites from water molecules. Credit: 2011 iStockphoto/akiyoko

The transport of ions is essential for the routine maintenance of the body. For this reason cells contain specialized enzymes that act as pumps that help ions to move around and pass through boundaries.

Now, Yuji Sugita at the RIKEN Advanced Science Institute in Wako, Japan, and colleagues have used to explain how one particularly important pump , Ca2+-ATPase, transports ions in muscle cells.

“The calcium ion pump is an essential membrane protein that can transport Ca2+ ions across biological membranes against a large concentration gradient,” explains Sugita. “It is believed to be related to some human heart diseases because there are large concentrations of the pump in the cell membranes of the heart, and the calcium ions work as messengers in .”

Specifically, each molecule of Ca2+-ATPase transports two calcium ions at a time from a cell’s cytoplasm into the sarcoplasmic reticulum (SR), a subcellular structure devoted to regulating calcium levels. By this method the SR releases when muscles are contracted, then reabsorbs them when muscles are relaxed.

Previous research has shown that Ca2+-ATPase on the SR membrane functions by switching between two states. First the binding sites face outwards and have high affinity for calcium in order to ‘gather’ ions from the cytoplasm. Then they face inwards and lose their affinity, thus releasing the ions into the SR.

To investigate exactly how this switching mechanism works, Sugita and colleagues focused on the role of a glutamate called Glu771, which is often found near the calcium binding sites. Studies have shown that when Glu771 is removed by mutation the calcium pump loses all its calcium-binding ability.

The researchers ran molecular dynamics simulations for both normal and mutant versions of the calcium pump. Their results revealed that the presence of Glu771 prevents water molecules from interfering at the (Fig. 1). In the Glu771 mutant, this system breaks down and the binding sites get flooded with water.

This is the first time that research has indicated a relationship between calcium binding and the shielding of water, the team notes. Sugita is hopeful that with the help of more powerful computers, he and his colleagues could soon simulate a full enzymatic cycle of the calcium pump.

“We are developing new algorithms that combine all-atom and coarse-grained models,” he says. “Using such multi-scale simulation methods, we hope to elucidate further molecular mechanisms of ion uptake by the calcium pump or other ion pumps.”

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More information: Sugita, Y., et al. Relationship between Ca2+-affinity and shielding of bulk water in the Ca2+-pump from molecular dynamics simulations. Proceedings of the National Academy of Sciences USA 107, 21465–21469 (2010). www.pnas.org/content/early/201… /19/1015819107.short

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kevinrtrs
1 / 5 (5) Feb 22, 2011
As more and more complex sub-systems are discovered in the body, it becomes less and less likely that evolutionary processes could have constructed human beings from mere molecules.
Isn't it amazing that highly intelligent people have the normal commonsense to know that complex, constructed or devised things take intelligence and organized[read non-random] effort to put into place.

Furthermore it's easier to break down things using random blows or savage attacks on them than it is to build those same things up. In fact you cannot build normal useful things using random undirected, disorganized processes. Seems like in this particular issue a lot of people have lost their commonsense.
Ethelred
2.3 / 5 (3) Feb 22, 2011
As more and more complex sub-systems are discovered in the body, it becomes less and less likely that evolutionary processes could have constructed human beings from mere molecules.
Nonsense. No one has found anything that could not evolve. Dr. Behe sure hasn't.
know that complex, constructed or devised things
Which is NOT what life is. It GROWS. It is NOT constructed.
Furthermore it's easier to break down things using random blows or savage attacks on them than it is to build those same things up
Yes. Destruction is always easier which is why my posts are longer and more complex than yours. Telling the truth is harder than making up nonsense.
In fact you cannot build normal useful things using random undirected, disorganized processes.
Note that word BUILD again. Life grows.

More
Ethelred
2.3 / 5 (3) Feb 22, 2011
And why do you constantly LIE about evolution being random It is long past the time that your Active Ignorance on the subject could excuse it.

Selection is NOT random. Constantly lying about won't make it so.

When was the Flood Kevin? How could even your Active IgnoranceTM accept such nonsense.

Ethelred
ryggesogn2 AKA Marjon on the Somali pirates.
The pirates are charging tolls for ships to cross their waters.
This stays till the end of the month when there is room.