How Protein Is Made Using Complex Information From Genes [DNA]


So, what are proteins?

In the body, there is a class of functionally sophisticated organic compounds called proteins. Proteins make up the most abundant molecule in living organisms.

Made from countless atoms, proteins are the most structurally complex molecule known.

In 1838, the Swedish chemist Jöns Jacob Berzelius (1779-1848) was the first person to use the word protein; it comes from the Greek word proteios that be translated into meaning “primary.”

Some claim it was Gerard Johann Mulder (1802-1880) who coined the word protein, also in 1838, but apparently Mulder received a letter from Swedish chemist (yes, that chemist) 20 days before publishing the word in a paper.

Regardless, these molecules are important for both structural and mechanical purposes.

Example:

Proteins are the cytoskeleton…

…which is akin to the human skeleton and provides the cellular scaffolding that gives the cell its shape…

…while also keeping that structure from deforming (there are some exceptions to this, but we will ignore that for now).

They also generate various ion channel receptors that turn chemical (and sometimes mechanical) messages into electrical signals.

Numerous hormones, neurotransmitters (ditto for their receptors), and immune system messengers are protein.

The same goes for the enzymes that regulate their chemical reactions without themselves getting consumed—although not all enzymes are proteins.

(The human body consists of roughly 1,500 different enzymes).

Put in another way:

Proteins are important in biological systems.

Something perplexing:

Humans, Proteins and Roundworms

When comparing humans to Caenorhabditis elegans (harking back to part one), we are only roughly 1,3 times more complex in terms of biological stuff.

Even more mind-boggling:

In comparison to Arabidopsis thaliana, or thale cress, humans are no more complex, counting the numbers of proteins.

Still, though:

We have yet to find a space rocket designed or built by the small flowering plant.

What is it about our biological makeup that creates differences in complexity between humans and thale cress?

Proteins Are Not Inactive Clumps

What generates the differences in complexity is how various proteins interact. Proteins are not passive clumps floating around in the body; they are binding to other molecules in a selective fashion.

This means that a given protein only binds to one up to a few thousand of the molecules that protein encounters.

Take for example the motor protein kinesin

In the human body, kinesin moves various molecules along microtubule filaments (which are made of yet another protein called tubulin).

Kinesin does this in a similar fashion like a locomotive ferrying cellular cargo along these so-called microtubules. 

Another example:

There are ion channels that allow various ions to pass through the otherwise (almost) impenetrable cell membrane, making ion channels proteins that span the entire cell membrane.

To regulate the current (ion flux), which would otherwise cause a significant imbalance of ions, special ion transporters, or pumps, send ions across the membrane against the electrochemical gradient.

This process is driven by the hydrolysis of ATP, or adenosine triphosphate, which coincidentally also drives the various kinesins.

What regulates these processes? 

Other proteins!

Question:

If proteins are so complex and regulate each other, what determines the function of these various proteins?

The Shape of Protein Determines Its Function

A key feature of proteins that is significant regarding their various functions is their different shapes.

Why?

That is because their shape differences determine their function.

Hormones, for example, all come in slightly unique shapes, with millions of copies of each hormone circulating in the bloodstream sharing an identical shape.

The same goes for that hormone’s receptor to which the hormones bind.

The receptors must have a complementary geometric shape to that of the molecule, say hormone, that lands on its so-called binding site.

  • A cliché in the field is that the molecule must fit its receptor like a key into a lock.

In other words, the shape of the protein is the key to its function.

But…

…what determines the shape and structure of proteins?

Amino Acids: The Building Blocks of Protein

Proteins are the common name given to a class of organic compounds that consist of long, unbranched chains of even smaller structural units.

These structural units are amino acids:

Amino acids, or α-amino carboxylic acids, exist in roughly 20 different versions in the human body.

They form various proteins, each of which has unique chemical properties.

In a given protein, its amino acids are the so-called monomers; mono is a prefix that means “single” or “only”—derived from the Greek word monos, which means “alone.”

The monomers are thus identical molecules binding together to create more complex structures.

These structures are called polymers; poly is the prefix that means “many”—it also originates from a Greek word (polus, or plural: polloi) that means “much” and “many.”

When amino acids come together to form longer chains of amino acids, like beads on a string, these chains are called peptides (between two to 50 amino acids).

When several peptides join together, they are thus referred to as polypeptides.

If the total number of amino acids surpasses 50, then that chain is called a protein.

For example:

The antioxidant glutathione is a peptide because it is built by three amino acids, whereas the hormone insulin is a protein because it consists of 51 amino acids.

To complicate things further:

There are several categories when it comes to peptides.

The peptides that regulate neural function, for instance, are referred to as neuropeptides; there are peptide hormones which are peptides acting as, well, hormones.

Makes sense?

Good!

Let’s dig deeper:

The Old Dogma of Amino Acids

There are nine essential amino acids that must come through the diet. And for the body to build the various proteins, outside the cell nucleus in structures called ribosomes, all the necessary amino acids must be present at the time of construction.

The dogma used to be that it is the amino acids that determine the shape of the protein, and thus its function.

In recent years, various other factors have come to play important roles in what the end protein looks like.

Temperature changes…

…fluctuations in ion concentration…

…together with other environmental variables…

…affect the shape of various proteins…

…and thus what kind of hormones, neurotransmitters, enzymes, and receptors one develops.

So what about complexity?

In other words:

How come humans are more complex than sea snails, roundworms, and/or thale cress given that we all share the same biological stuff?

Let’s find out!

10⁴⁰⁰ Possible Amino Acid Sequences

Each protein has unique amino acid sets. In the human cell, there are several thousand forms of proteins. The majority of proteins are roughly 300 amino acids long, but they come in all shapes and sizes, ranging from 50 to 2,000 amino acids.

If we crunch those numbers, looking at 20 different amino acids, the number comes out as 10⁴⁰⁰ possible sequences.

That is CRAZY!

To make it even more complex:

Proteins are so accurately built that changing even a few atoms in one amino acid can mess up the entire structure of that molecule to such an extent that it obliterates its function.

Put another way:

Alter a few atoms in one(!) amino acid, in one sequence out of 10,000 possible sequences (plus 397 more zeros), and it can sabotage the entire function of that molecule.

It seems as though minimal changes can cause huge effects when it comes to amino acids and subsequently to proteins.

Let’s have a closer look:

Protein Domains & Domain Shuffling

Most large proteins generally consist of several distinct domains called protein domains. Protein domains are substructures of protein that are produced by a continuous folding that occurs independently of the rest of a given polypeptide, resulting in a compact structure that is highly stable.

A protein domain is generally 40 to 350 amino acids long, but even a small protein domain is highly complex.

So:

How come humans are more complex than fruit flies and roundworms?

The answer has to do with a process called domain shuffling.

Domain shuffling is an evolutionary process in which several large proteins evolved through the linking of preexisting protein domains in novel combinations.

Thus, new possibilities of interaction.

The vertebrate evolution resulted in the emergence of several new versions, or combinations, of protein domains.

Put another way:

The result of this complex and tedious process resulted in the fact that there are in the human body almost twice as many protein domain combinations compared to that of a roundworm.

(For an in-depth discussion, see Diana Kwon’s writing here)

What this means is that this complexity says something about the possibilities for various proteins to interact.

In other words:

The key is not how many proteins attend the party, but how well they mingle.

Conclusion

Somewhere around here, one needs to sit and ask:

If the amino acids sequence decides protein shapes…

…and proteins make us who we are…

…what determines the chain of amino acids that results in the proteins that make up our various neurotransmitters (their receptors), hormones, and (some, but not all) enzymes?

Stay tuned for the third part!

References

Alberts, B. et al (2015). Molecular biology of the cell. 6th ed. New York: Garland Science.

Binarová, P. & Tuszynski, J. (2019). Tubulin: Structure, Functions and Roles in Disease. Cells (Basel, Switzerland), 8(10), p.1294.

Editors of Encyclopedia Britannica (2018). Adenosine triphosphate | Definition, Structure, Function, & Facts. In: Encyclopædia Britannica. [Online].

Institute of Medicine (US) Committee on Military Nutrition Research. (1999). The Role of Protein and Amino Acids in Sustaining and Enhancing Performance. Washington (DC): National Academies Press (US); 1, Committee Overview.

Johansson, U. (2014). Näring och Hälsa. 3rd edition. Lund, Sweden: Studentlitteratur.

Koester, J. & Bean, B. (2021). Ion Channels. Kandel, E. et al. Principles of Neural Science. 6th Edition. New York, USA: McGraw Hill. pp. 165-189.

Kwon, D. (2015). What Makes Our Brains Special? [Online] Scientific American.

Science Direct. (2021). Protein – an overview | ScienceDirect Topics. ‌

Wikipedia Contributors (2019). Jöns Jacob Berzelius. [Online] Wikipedia.