Salt Bridges And Potassium

Potassium in your food matters because your cells need enough of it to function properly. You need enough inside your cells to balance the sodium outside your cells. Your cells do their work by changes in the electrical field produced by moving potassium and sodium around. The changes in the electrical field change the shape of proteins in the cell. When the shapes of proteins change, your cells can extract energy from fuel (food), they can make cell structures, and they can unveil genes and translate genes.

In the last post we discussed how structural changes in the VSD of the gate that opens and closes potassium channels can affect how fast potassium can balance with sodium. Slight changes in the electric field of a cell can cause a difference in the shape of the VSD protein. This change in shape will allow potassium to flow through the channel or will stop it from flowing through.

Protein Molecules' Shapes

Salt Bridge ChangeThe main determination of the shape of a protein is the sequence of amino acids in the protein. But there are multiple other factors determining the shape. Two major factors are the large cellular electrical field produced by sodium and potassium, and the smaller local electric fields within the protein.

The local electrical fields in a protein come from its amino acids. These fields are determined by the charges on the amino acids in the protein, by the distances between these local charges, and by any ions in the local field.

The force of the larger cellular electric field that the protein sits in is added to the local field forces. Thus this larger electric field influences the strength of local electric field forces, such as hydrogen bonds, salt bridges, electrostatic forces, and other local forces that give rise to the ultimate shape of the protein.

How A Protein Does Its Work

The last post discusses the importance of salt bridges in the function of the VSD. A change in position of six salt bridges in the VSD occurs when there is a change in the electric field across the membrane that the potassium channel sits in. This field change is created by movement of potassium and sodium across the membrane. This causes the protein's shape to go back and forth, and perform its function of opening and closing gates on the potassium channel.

But you do not need to change multiple salt bridges to affect how a cell functions. A change in just one salt bridge is enough, as discussed in a recent study (1). Especially when the change results in a permanent structural change in a protein.

Severe Bodily Changes From A Salt Bridge Change

This recent study (1) of a salt bridge in an important nuclear protein showed a connection between the severity of a molecular change in the protein and the severity of what happens to a person's body.

The structural protein (lamin A) that was affected is produced by the LMNA gene. Just like the VSD protein, it is also affected by the charge inside and outside the cell. This protein provides the structure of the nucleus of the cell, and plays a role in the function of the chromosomes. Its structure was changed when a single salt bridge in the protein was changed.

A salt bridge is a very small bond between 2 molecules that is not as strong as a covalent bond. It is composed of a hydrogen bond and an electrostatic bond combined. This post discussed how important salt bridges are in the potassium channels and pumps in cell membranes. Small changes in the electric field that the VSD of a potassium channel sits in changes its six salt bridges and its shape, so channel can do its work.

However a change in the local electric field of just one salt bridge can result in severe changes to a person's entire body. This study showed that changing one salt bridge can result in massive skeletal abnormalities with an undergrowth of the jaw and collarbones. It can also result in thinning of the bones in the fingers, delayed closure of bony parts, overcrowding of teeth, thinning of the skin, growth retardation, and severe metabolic abnormalities such as lipodystrophy, insulin resistance, diabetes, and hypertriglyceridemia. All of this from a single amino acid change in a protein, resulting in a change in the strength of a salt bridge.

In this particular study, the researchers found 3 different types of changes in a single salt bridge of the protein lamin A. The researchers had 3 patients, each of whom had a change in a single amino acid at position 527 in the protein. This position normally has arginine. By predicting the strength of the salt bridge, they were able to predict how much of a change would occur in a patient's tissues and organs.

Salt Bridge Changes

In the first case, leucine replaced arginine and led to loss of the salt bridge. Using computer modeling, the researchers predicted severe changes to the patient's body because the protein structure was destabilized.

In the second patient, histidine replaced arginine, resulting in a weaker salt bridge, but not a loss of the salt bridge, as occurred in the first case. The researchers predicted that the structure of the protein would be destabilized, but less so than with leucine. This led to less severe bodily changes than occurred in the first case.

The third patient had a substitution of arginine with cysteine, which led to a disulfide bridge. This resulted in complete structural change of the protein and led to the most severe bodily change.

Thus with a computer modeling system from multiple bioinformatics sources, the researchers were able to predict the severity of the effect on a person from the severity of the effect on a protein. The effect on the protein came from the physical forces involved in a single salt bridge in a single structural protein. The researchers found that the more severe the change in physical forces between molecules, the more severe the effect on the patient.

Why The Study Is Important

This article shows the importance of the electric field that is created by the potassium and sodium concentrations inside and outside our cells. Small changes in this large electric field change the local fields in our cells' proteins. These changes back and forth in local electric fields are how our cells do their normal work.

If the large electric field from potassium and sodium is too strong or too weak, the local electric fields may not be able to change adequately. If the local fields cannot change adequately, the protein cannot change shape enough to do its work. When this happens, the cell does not function well, and we do not function well.

Keep your cells functioning well by keeping a good balance of sodium and potassium inside and outside your cells. Eating meals with a high potassium sodium ratio is the best way you can provide your cells with what they need to function well.

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1. A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome. Al-Haggar M, Madej-Pilarczyk A, Kozlowski L, Bujnicki JM, Yahia S, Abdel-Hadi D, Shams A, Ahmad N, Hamed S, Puzianowska-Kuznicka M. Eur J Hum Genet. 2012 Nov;20(11):1134-40. doi: 10.1038/ejhg.2012.77. Epub 2012 May 2.

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