Unfolding the Mystery of Proteins:
Structure, Function and Impact

The elegance of protein design

Proteins are the molecular foundations of life! They do everything from speeding up chemical reactions to giving our cells their shape and structure. But what makes them so versatile? It all comes down to their unique structure, which determines how they function. In this article, I’ll explore how proteins are built, how their structure relates to their function, and why even small changes can have dramatic effects.

The building blocks: amino acids and peptide bonds
All proteins are composed of amino acids, a monomer that links together to form polypeptide chains. There are 20 standard amino acids, each with a central carbon (the alpha carbon), an amino group (-NH2), a carboxyl group (-COOH), and a variable R group. It’s the R group that determines an amino acid’s properties — whether it’s hydrophilic, hydrophobic, acidic, or basic.

Proteins are remarkable molecules, balancing complexity with precision. Their structure, from simple amino acid sequences to sophisticated multi-subunit arrangements enables life’s most intricate processes. We, as scientists, continuing to study proteins, unlock deep insights into health, disease, and biotechnology, opening doors to new treatments and innovations.

Fun fact: we have all heard the paradox, ‘What came first, the chicken or the egg?’ Although this is still not definitively resolved and some scientists might not agree on one answer, from a molecular biology perspective, the egg came first! Here’s why:

The hard eggshell of a chicken egg is formed using a protein called ovocleidin-17 (OC-17), which is found only in hens. However, for a chicken to exist, it must hatch from an egg. This suggests that a proto-chicken (a bird very similar to a chicken but not quite the same species) laid an egg containing a genetic mutation that created the first true chicken. Since the egg existed before the chicken inside hatched, the egg came first!

So, proteins like OC-17 played a key role in the evolution of modern chickens - making this classic paradox a little less mysterious.

Amino acids are linked by peptide bonds through a condensation reaction, where a molecule of water is released. This linear sequence of amino acids forms the primary structure, which serves as the foundation for all higher levels of protein structure.

Primary structure
The sequence of amino acids in a polypeptide is determined by the genetic code. A single mutation in this sequence can be life-altering. For instance, let’s consider sickle cell disease, where a single amino acid substitution in haemoglobin causes the protein to form rigid fibres, distorting red blood cells and affecting their ability to function correctly.

Secondary structure
As soon as a polypeptide chain forms, it stars to fold into regular structures due to hydrogen bonding. The two most common types of secondary structures are:
  Alpha helices: coiled structures stabilised by hydrogen bonds between every fourth amino acid. Found in keratin (hair, nails) and membrane-spanning proteins.
  Beta pleated sheets: zigzag arrangements of polypeptides, held together by hydrogen bonds. Found in fibroin (silk) and many enzymes.

Enzymes as biological catalysts
Enzymes speed up biochemical reactions by lowering the activation energy required for a given reaction. In terms of chemistry, this means more particles will have enough energy to perform successful collisions, increasing the rate of the reaction. Enzymes specificity arises from their unique active sites, which follow the induced fit model. The induced fit model is the accepted theory that enzymes undergo slight conformational changes to accommodate substrates. Namely, DNA polymerase, which accurately replicated DNA.

Structural proteins
  Collagen provides tensile strength to connective tissues.
  Keratin forms protective structures like skin and nails.
  Actin and myosin drive muscle contraction, showcasing how protein structure enables dynamic function.

  Haemoglobin binds and releases oxygen efficiently, thanks to its quaternary structure and allosteric regulation

  Membrane proteins like ion channels control cellular communication and homeostasis

  Insulin, a hormone, binds receptors to regulate glucose uptake

Figure 1: general amino acid structure

Though it is heartbreaking to attribute such life-altering conditions to tiny mutations in one of the simplest structures in our bodies, understanding these failures has led to breakthroughs in medicine, including drug design targeting protein structure.

The precise folding of proteins is crucial as errors can lead to devastating consequences:

  Prion diseases like Creutzfeldt-Jakob Disease occur when incorrectly folded proteins induce normal proteins to misfold, leading to brain damage, and causing dementia, involuntary muscle movements, loss of intellect and coordination, changes in personality and slurred speech. Lots of people with Creutzfeldt-Jakob Disease die within a year of symptom onset.

  Cystic fibrosis results from a mutation in the CFTR protein, which is responsible for maintaining proper hydration and mucus function in various organs, especially the lungs. This mutation disrupts ion transport in cells, resulting in thick, sticky mucus buildup in the lungs and other organs. People with cystic fibrosis often experience recurring chest infections, difficulty gaining weight, frequent coughing, and wheezing.

The tertiary structure results from further folding, driven by interactions between the R groups:

  Hydrophobic interactions push non-polar side chains to the protein’s interior.
  Ionic bonds form between charged R groups.
  Disulphide bridges are covalent bonds between cysteine amino acids, they create strong structural reinforcements.
  Hydrogen bonds contribute to stability and specificity.

The 3D shape is vital. Enzymes, for example, have active sites precisely shaped to bind substrates. Incorrect folding at this stage can lead to diseases like Alzheimer’s, where incorrectly folded proteins aggregate into plaques, interfering with brain cell function, leading to memory loss, impaired thinking, and eventually an inability to perform daily tasks.

Some proteins are multiple tertiary structures joined together, they function as multi-subunit complexes. Such as haemoglobin, which consists of four polypeptides working together to transport oxygen. The quaternary structure allows for cooperative interactions, enhancing function.
Conjugated proteins also have one or more non-protein parts to the molecule, like haemoglobin’s ‘haem’ group.
(See Figure 4)