# What is the secondary structure distribution per AA in the Human proteome?

If one would classify each amino acid to either be in a Coil, Beta strand or Alpha helix what would be the distribution of these classes in the human proteome?

Is it 33%-33%-33% or is it biased? If it is biased why?

I thought it should be around equal, but I run the whole proteome through PSIPRED, and I found the distribution to be 60% Coil, 30% Helix, 10% Sheet. Why is it so?

• I'm not sure what you're asking here. You seem to have answered your own question about the distribution (interesting, by the way!). So, by your own data, it is obviously biased. I don't know much about proteins, I'm a genomics person, but why would you assume no bias? Also, are you looking percent of total amino acids? Percent of total protein in each conformation? A bit more detail would be helpful. Mar 14, 2017 at 12:59
• A percent of amino acids in each secondary structure. I am just not really believing by own results, as far as i remember from the university these should be near equal (or like little bias). there are aprox 20k proteins in the human proteome, if we say each consist of 500 AA, we roughly get 10 million amino acids, which is in contrast with my results, as i get 6 million AAs in coils, 3 million in helix, and 1 million in sheets. Mar 14, 2017 at 13:42
• While I strongly object to the tone of the answer you've received so far, I see no reason whatsoever to assume an equal distribution. The properties of the different structures are not the same, so it doesn't make sense to expect such a distribution. Some explanation of why you would make such an assumption might be a helpful addition to your question. Mar 14, 2017 at 14:01
• The only answer I could give is very vague, unfortunately. The distributions are not equal because these three SSE types play quite different roles in 3D structures. Sheets usually form in the core of a folded structure, and are short. Helices tend to pack around the outside, and can be longer. 'Coil' is everything else, and covers structure like long loops. Mar 14, 2017 at 16:28
• A major problem with my answer is the distribution of folds. If genomes were packed full of helical bundles, then the proportion of helix would go up. Presumably an organism with a lot of excreted extracellular proteins (that tend to have little secondary structure) would have a higher proportion of coil, and so on. Mar 14, 2017 at 16:30

The question asks why the distribution of coil, alpha-helix and beta-strand is 60:30:10 rather than 33:33:33. The answer is:

“Why not”

This is because there is no reason whatever to expect that three types of structure (or in the case of coils, lack of structure*) should be present in equal amounts in proteins. It is like expecting that the percentage intron, exon and ‘junk’ DNA should be equal, or that the percentage of fuel reserves stored as glycogen and fat should be the same. Yes, they belong to the same category, but they are sufficiently different in each case for one not to be surprised if they are not required in equal amounts.

To understand this one needs to look a little more carefully at the occurrence of alpha-helix or beta-strand conformation in the three-dimensional structure of proteins. Three points may be emphasized:

• Amino acids have particular conformations because they are part of an extended helix or sheet of strands the entirety of which leads to its structural stability — you don’t have a random mixture.
• In many cases the helices or sheets are occur in particular combinations to give a family of proteins of similar overall structure. Again, the idea of random mixtures doesn’t enter into the equation.
• These overall structures are suited to particular functions, so the abundance of proteins from a particular structural family will be determined by the requirement for antibodies or ion transporters or signal transducing proteins etc., not by some shake of the dice.

Images illustrating two such families are shown below:

(a) shows an ion transport proteins, predominantly alpha-helices, whereas (b) is an immunoglobulin domain with a distinctive pattern of beta strands (as well as some helix). For further examples and information I suggest the EMBL on-line course on protein classification and Berg et al. online, for example Section 7.3.

*Footnote 1: Situations where equal occurences might be expected It is worth while contrasting the situation with protein secondary structure to some where the prior expectation might well be for equal usage, and the deviation from this could be regarded as bias and an explanation worth asking for:

• The different proportion of the 20 amino acids in proteins (although a chemist would not expect equal proportions)
• The different usage of synonymous codons of the genetic code in various species and mRNAs
• The different usage of the similar molecules with a high phosphoryl group transfer potential: ATP, GTP, UTP and CTP (often loosely termed ‘high-energy’)

*Footnote 2: A coil is not a secondary structure

As is stated in the Wikepedia entry for Protein Secondary Structure:

The random coil is not a true secondary structure, but is the class of conformations that indicate an absence of regular secondary structure.

It might be mentioned in regard to protein structure that there are smaller three-dimensional motifs that the analysis quoted does not consider. These do not occur in equal proportions either, to nobody's great surprise.

• Votes on a question have nothing to do with "sharing the mistaken scientific logic of the question". All due respect, get off your high horse. I upvoted it because I felt the underlying questions (why is such a distribution observed? Why are coils more common?) to be both interesting and worth investigating. Sadly, your answer doesn't address anything in the question apart from the obviously faulty premise. Mar 14, 2017 at 13:55
• This is not an answer i am sorry. This is a rhetorical something. I remember something from the university that the percentages of secondary structures are kind of equal. This must be a long known fact (either true of wrong) and all i want is a confirmation. Mar 14, 2017 at 13:58
• David, I see from your profile that you've done some structural work. Why don't you improve this answer and actually add something about the relative stability, functional plasticity or any other relevant properties that are different in the different protein conformations and how these can be used to explain the observed ratio? Mar 14, 2017 at 13:59
• @terdon — I'll stay where I am, I'm quite comfortable. I certainly answered the question. The reason that they differ from random — that was the question — is because there is no reason they should be random. If the question had been why is there more helix than sheet in proteins I would have voted to close as the answer is a matter of opinion. All you get is the sort of circular argument about something having more general utility. The poster needs to get away from his computer and read about proteins. Mar 14, 2017 at 14:02
• @GáborErdős — Your memory from the university is either faulty or you were told untruths. It is not a fact — long known or otherwise. If you do not believe me I suggest you search the internet (or read some books) to find evidence for this and cite it in your question. Mar 14, 2017 at 14:06