Forms Of Vitamin D-binding Proteins

You don't actually require vitamin D in your diet, because your body can synthesize it with the aid of a little sunshine. The active form is 1,25-dihydroxycholecalciferol, a highly lipophilic or fat-soluble molecule that gets around in the blood with the aid of a molecule called vitamin D-binding protein. This protein helps ferry the vitamin D to its end destination.

Polymorphism

The vitamin D-binding protein is polymorphic, meaning there are multiple versions or forms of the protein encoded by different variants or alleles of the same gene. The three common alleles are GC2, GC1F and GC1S. Part of the proteins produced by the last two alleles are glycosylated, meaning they have a sugar molecule attached to one of the amino acids in the chain. These alleles are codominant, meaning that both will be expressed, and hence a person who inherits two different alleles will have two different versions of the protein.

Primary Sequence

There are some slight differences in the amino acid sequence between the three common alleles. GC2 and GC1F have an amino acid called aspartic acid at position 416, compared to a glutamic acid in the GC1S allele. GC2 has a lysine amino acid at position 420, compared with the amino acid threonine in the other two. The threonine is the site where the sugar is attached in the glycosylated proteins encoded by GC1F and GC1S.

Function

It's not clear at present whether these differences in the form of the vitamin D-binding protein have any clinical or physiological significance. Scientists do know, however, that the vitamin D-binding protein performs two other functions in addition to binding vitamin D. It helps to stabilize G-actin in blood plasma, thereby preventing formation of filaments that might damage the capillaries. It also binds to immunoglobulin G and is involved in the immune response.

Other Features

Overall, the vitamin D-binding protein has some 458 amino acids. The part of the protein that binds vitamin D is lined by amino acids that have hydrophobic, or "water-fearing," side chains; these properties ensure the protein has a high affinity for the rather hydrophobic vitamin D. Once vitamin D has been transported to its final destination, it binds to a receptor inside the cell called the vitamin D receptor, or VDR, which acts to turn on or off important genes.