What Are Is The Structural Hierarchy Of Proteins?

Consider n unique books arranged on a bookshelf. To arrange the books on this bookshelf, there are n books that can go in position 0, on the very left of the shelf. In the next position, directly to the right of position 0, position 1, 1 of the n-1 remaining books can be placed. In the next position, position 2, 1 of the remaining n-2 books can be placed.

Following this pattern, it`s clear that there is a choice of n-k books to go in position k. The number of ways of arranging the bookshelf overall is then n*(n-1)*(n-2)*...*2*1 = n! . There are n! ways of arranging n unique books on a bookshelf.

Test: let there be 3 unique books: Animal Farm ("A"), The Bible ("B"), and The Catcher in the Rye ("C"). There are 6 different ways of arranging these on the bookshelf: "ABC", "ACB", "BAC", "BCA", "CAB", "CBA". 3! = 3*2*1 = 6, which is consistent with the true result.

What about if there are 2 unique books? Then there are 2 ways of arranging these ("AB" and "BA") and 2!=2. What about 1 book? Only way to arrange this is "A" and 1!=1. What about 0 books? There is again only 1 way to arrange this: " ", where the bookshelf is empty. Therefore 0!=1.

Every organism on Earth is made of complex macromolecules that have individual structures that relate to their function. Proteins are among the most important molecules that make up organisms.

Proteins are synthesised in the process of Translation in which Ribosome molecules and Transfer Ribonucleic acid (tRNA) synthesize polypeptide strands of Amino Acid monomers. The amino acids join in condensation reactions between the amino group of one amino acid and the carboxyl group of another to form a peptide bond.

There are two main types of protein: Globular Proteins and Fibrous proteins. Globular proteins are spherical in shape and fibrous proteins are long and thin. Amongst the most numerous type of protein are Enzymes. Enzymes are biological catalysts that accelerate the rate of chemical reactions in the body.

Proteins have a structural hierarchy in which they start as linear chains of amino acids and can fold to create complex three dimensional structures.

There are 20 naturally occurring amino acid residues in the human body that join together in different orders to from polypeptide chains. The backbone of a polypeptide strand is universal in all proteins and consists of an amino terminus at the start and a carboxy terminus at the end. Every amino acid has the same 3 components an amino group, a carboxyl group and a hydrogen atom. The R group or ‘side chains’ is what differs in each amino acid and gives the protein its characteristic bonds and properties.

The first structure that the amino acids make once they bind to form a single polypeptide strand or ‘sub unit’ is called the protein Primary Structure. This structure is simple with the peptide bond being the only bond holding the linear structure together. The primary structure is not folded and is described as being monomeric due to the presence of only one subunit.

Within the polypeptide, interactions can from between the amino group of one amino acid and the carboxyl group of another. This can from hydrogen bonds that span the back bone of the polypeptide. Such interactions can cause the protein to take on a new conformation a Secondary Structure. The most common secondary structures are α helix and β pleated sheets. The polypeptide strands that make up an α helix are usually orientated in the same direction and so take on an parallel structure. In a β pleated sheet, adjacent parts of the polypeptide chain can run in opposite directions but the chain can also double back on itself and so is said to take on a parallel and antiparallel conformation.

A protein secondary structure can contain more complex folds that occur as part of the overall protein molecule. Proteins that adopt this conformation can have different sections that adopt different secondary structure motifs. This overall 3D structure is called the protein Tertiary Structure. The degree of folding in the polypeptide is dependent on the covalent and non-covalent interactions between the R Groups of different amino acids in the polypeptide. These interactions form bonds that allow complex folding to occur. The R groups of individual amino acids can be charged, polar, non-polar or able to form hydrogen bonds. For example, hydrophilic charged or polar groups in amino acids that are exposed on the surface of the folded polypeptide can interact with water molecules via hydrogen bonds or ionic interactions. Covalent bonding can occur between amino acids that form strong Disulphide bridges along the polypeptide. These bonds occur between Sulphur atoms of different cysteine amino acids in the protein. These bonds allow the protein to adopt a strong and stable conformation.

Proteins can me multimeric and so be a made of more than one subunit. This is called the protein Quaternary structure and depends on covalent and non-covalent interactions between the surfaces of folded subunits. The multiple subunits that make up the protein can be homomeric and so be identical to each other or heteromeric and so be different to one another.

The enzyme Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) is a monomeric protein that catalyses glycolysis during respiration in which the sugar glucose is broken down. It is made of four identical subunits. Each GAPDH subunit associates with Nicotinamide Adenine Dinucleotide (NAD) which is reduced during cellular respiration.

The globular protein Haemoglobin is an example of a multimeric protein. Is contains 4 subunits two α subunits and two β subunits. It is responsible for binding to oxygen in the blood and transporting it to respiring muscles in the body.

An in vivo environment such as that of the human body contains complex proteins which sometimes require assistance when folding to form a stable conformation. Chaperone proteins can assist in this folding process by preventing inappropriate interactions between R groups of individual amino acid residues. Chaperones can refold proteins that have misfolded.

Within proteins, single polypeptide strands can have multiple functions. The different areas of a polypeptide strand dedicated for different functions are called domains. These domains are usually vital to the direct functioning and purpose of the protein. An example is the enzyme Pyruvate Kinase which has 3-4 domains that allow it to complete its function of catalysing the final step of glycolysis (EMBL EBI 2018).

Proteins can be post translationally modified so that co factors can be added to the protein. These co factors or prosthetic groups can be a variety of molecules and ions but most commonly are sugars and lipids. These are added to the protein in a process called Glycosylation and Lipidation. The prosthetic groups are vital to a proteins function. An example of a protein associated with a cofactor is Haemoglobin. The four sub units that make up Haemoglobin each associate with a Haem group. Each Haem group has an Iron molecule attached to it. It is at this iron molecule that oxygen binds.

There are a number of techniques that allow scientists to study the structure and function of proteins. One method called X-Ray Diffraction allows scientists to construct three-dimensional electron-density maps of protein molecules. Firstly, the protein is arranged to form a crystal by adding the protein into a salt solution. A narrow beam of electrons is fired at the protein. Some of the charged particles go straight through the protein but some are scattered. Scattering depends on the atom arrangement of the protein. A computer is then used to construct three-dimensional electron-density maps from the scattering. The maps can be used to produce a molecular model of the protein.

Proteins are complex organic molecules that carry out a many functions within the body. They can have a huge diversity of structures and these structures rely upon the complex interactions of amino acid R groups. Proteins have a hierarchy of structure in which the most simple is the primary structure which a protein inhabits when it is synthesised straight after translation. The next two levels of hierarchy the secondary and tertiary structure of a protein is characterised by the addition of bonds as a product of further folding. Once a protein has a stable conformation, it can associate with other subunits and become a multimeric protein, adopting a quaternary structure.

Proteins are vital to the survival or organisms as they carry out important cellular and metabolic processes. The simplest prokaryotes show great similarities in protein coding regions to eukaryotes denoting how important proteins are as they have been carried through generation to generation via natural selection. (1260)