The Biological Functions of Proteins [Genes & Behaviors: II]

In the process of sequencing the human genome, the results, although breathtaking, has revealed that the human body containts roughly 19,000–21,000 genes that code for a particular protein.

A majority, about 18,000, of these genes are thought to be expressed in the brain.

If we compare the mere numbers, humans are no more complex than arabidopsis thaliana (thale cress)…

…or approximately 1,3-fold as complex as the previously mentioned C. elegans with its 13,000 genes and 1,000 cells of which 300 are neurons.

Yet:

Here we are, thinking that we humans are at least, to some extent, more complex than thale cress.

These insights raise some important questions:

  • What is a protein?
  • What does it mean that a gene codes for a particular protein?
  • What do all the genes that do not code for a protein do?
  • And how are humans still more complex than a roundworm or thale cress (it’s so much fun to bring that up)?

To begin the journey toward untangling the question of how much of our genes mediate complex human behaviors…

…we must first get a grasp of how proteins work in the biological system that is the human body.

Why?

Because proteins make us who we are.

Keep reading!

What is the Biological Function of Protein?

Proteins are complex macromolecules made from countless atoms. They are the most abundant class of organic compounds in biological systems with many vital mechanical and structural functions, working both in isolation and in combination with other proteins.

However:

Proteins are not inactive clumps; they actively bind to other molecules…

…and they do so in a rather selective fashion in that proteins only bind to one or a few of the many thousands of molecules they encounter.

Evidence:

Many neurotransmitters, hormones, and messengers of the immune system are proteins.

As well as enzymes, the catalysts for biochemical reactions — although not all enzymes are proteins.

Proteins also provide the cell’s structure, akin to the human skeleton.

Certain specialized proteins act as toxins or antibodies, while some proteins function as signal integrators, relaying signals toward the nucleus from the cell membrane.

Other proteins are motor machines, such as kinesin:

Kinesin moves along microtubule filaments (made of yet another protein called tubulin) like a locomotive ferrying cellular cargo along the microtubules.

Proteins also organize the intracellular environment through complex processes.

The channels on the cell membrane that allow various ions to pass through the otherwise (nearly) impenetrable membrane are proteins…

…dito for the ion transporters, or pumps, moving ions against the electrochemical gradient to maintain osmotic equilibrium.

What regulates these ion pumps?

You guessed it:

Other proteins!

Protein Structure Determines Function

An essential feature of proteins is their shape because that is what determines their function. Various hormones with different effects each their unique shape, with millions of copies of each particular hormone in circulation, all sharing the same shape…

…and the receptor to which neurotransmitters and hormones bind must have a complementary geometric shape to that of the molecule that lands on the binding site.

A cliché is that the molecule fits to its receptor like a key into a lock.

So, the shape of a protein is litteraly a key to its function…

…but…

…what determines the protein’s structure and shape?

Amino acids!

What are Essential Amino Acids?

Proteins are long, unbranched chains of structural units called amino acids — short for α-amino carboxylic acids. There are about 20 different amino acids in proteins that make up the human body, each of which comes with different chemical properties.

Amino acids are the monomers of protein, a molecule binding to other identical molecules to produce a polymer; the prefix “poly” means many.

The monomers then join together to form a polypeptide chain.

Proteins are thus also known as polypeptides (chains of amino acids)…

…and peptides that enable neuronal communication are named neuropeptides.

A peptide consists of one or more amino acids (up to 50 amino acids) linked together by chemical bonds.

Yet:

As “per yoozh” what it comes to science…

…in some cases…

…one protein is the result of several polypeptides combined together.

We can thus think of a peptide as a short version of a protein.

In less fancy language, we are talking about amino acids organized in a particular way to create a protein with a specific shape…

…and thus a specific function.

A common way to describe this relationship is that amino acids are like beads on a string.

Although, again, science is usually not that straightforward:

The dogma was that the string (or sequence) of amino acids decides the structure of a given protein…

…although temperature, the concentrations of ions and various other environmental factors have been discovered to also affect the shape of the various proteins.

This is where complexity emerges.

The Unique Characteristics of Humans — Protein & Amino Acids

Each protein has a unique set of amino acids. In the cell, there are many thousands of forms of proteins. Most proteins are roughly 300 amino acids long; they come in all shapes and sizes, ranging from 50 to 2,000 amino acids.

With 20 types of amino acids, we are looking at 10⁴⁰⁰ possible sequences.

No, no, no.

Read that again!

That is CRAZY!

10⁴⁰⁰ possible sequences.

To make things even more complicated:

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

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

🙄

😮

🤯

Let’s all take a deep breath before we move on.

Ready?

Okay, let’s move on.

How Complexity Emerges (Or Why We Are More Complex Than Thale Cress)

Large proteins usually consist of so-called protein domains. They are self-stabilizing, structural units of the protein’s polypeptides that fold more or less independently from the rest of its polypeptide companions.

In the process of sequencing the human genome, scientists revealed that vertebrates inherited nearly all their proteins from invertebrates; roughly seven percent of the domains in humans are vertebrate-specific.

So, why are we more complex than thale cress?

The answer:

Through a process called domain shuffling, the vertebrate evolution generated several novel protein domain combinations.

As a result, humans carry almost twice as many domain combinations compared with C. elegans or Drosophila melanogaster, enabling humans to have more ways for proteins to interact.

In other words:

  • It is not a matter of how many proteins there are at the party; it is about how they mingle with each other.

And apparently, thale cress does not mingle at parties.

This gives us some clues as to what makes us human, in terms of protein-protein interactions.

How Proteins Make Us Human

These findings point to an answer regarding differences in complexity between humans and other animals, even though all share the foundational building blocks.

In fact, comparing the human genome to that of a roundworm or the common fruit fly, Drosophila melanogaster, Michael Stumpf and colleagues found that…

“…the human interaction network is one order of magnitude bigger than the Drosophila melanogaster interactome and 3 times bigger than in Caenorhabditis elegans.”

Hurray!

Human proteins mingle better than both worms and flies.

And to further marvel at the complexity of human biology:

There is still little to no knowledge regarding the function of over 10,000 of the proteins in the human genome.

This is mind-boggling and humbling, to say the least.

So, with this knowledge in our heads…

…at some point, one must sit down and ask:

If the string of amino acids decides the shape of proteins, and proteins make us who we are, what determines the amino acid sequence that results in the proteins that make up our neurotransmitters, hormones, and (some, but not all) enzymes?

Stay tuned for part three!

References.

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A curious psychology student, publicly learning how the brain mediates complex behaviors.

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Christoffer Hagenmalm

Christoffer Hagenmalm

A curious psychology student, publicly learning how the brain mediates complex behaviors.

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