How ‘simple’ can a protein be and still have a significant biological effect

Words only have meaning in the context of the much larger collection of words we call language. So it is with proteins. Their only ‘meaning’ is the biologic effects they produce in the much larger collection of proteins, lipids, sugars, metabolites, cells and tissues of an organism.

So how ‘simple’ can a protein be and still produce a meaningful effect? As Bill Clinton would say, that depends on what you mean by simple. Well one way a protein can be simple is by only having a few amino acids. Met-enkephalin, an endogenous opiate, contains only 5 amino acids. Now many wouldn’t consider met-enkehalin a protein, calling it a polypeptide instead. But the boundary between polypeptide and protein is as fluid and ill-defined as a few grains of sand and a pile of it.

Another way to define simple, is by having most of the protein made up by just a few of the 20 amino acids. Collagen is a good example. Nearly half of it is glycine and proline (and a modified proline called hydroxyProline), leaving the other 18 amino acids to make up the rest. Collagen is big despite being simple — a single molecule has a mass of 285 kiloDaltons.

This brings us to [ Proc. Natl. Acad. Sci. vol 112 pp. E4717 – E4727 ’15 ] They constructed a protein/polypeptide of 26 amino acids of which 25 are either leucine or isoleucine. The 26th amino acid is methionine (which is found at the very amino terminal end of all proteins — remember methionine is always the initiator codon).

What does it do? It causes tumors. How so? It binds to the transmembrane domain of the beta variant for the receptor for Platelet Derived Growth factor (PDGFRbeta). The receptor when turned on causes cells to proliferate.

What is the smallest known oncoprotein? It is the E5 protein of Bovine PapillomaVirus (BPV), which is an essentially a free standing transmembrane domain (which also binds to PDGFRbeta). It has only 44 amino acids.

Well we have 26 letters + a space. I leave it to you to choose 3 of them, use one of them once, the other two 25 times, with as many spaces as you want and construct a meaningful sequence from them (in any language using the English alphabet).

Just back from an Adult Chamber Music Festival (aka Band Camp for Adults).  More about that in a future post

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