Brent Cornell

Proteins are a class of molecules that enact the genetic instructions within a cell and carry out a diverse array of functions

• Fibrous proteins are generally composed of long and narrow strands which are insoluble in water and have a structural role
• Globular proteins generally have a more compact and rounded shape, they are soluble in water and have functional roles 

Amino Acids

Proteins are comprised of long chains of recurring monomers called amino acids, which all share a basic structure:

• A central carbon is bound to an amine group (NH₂), a carboxylic acid group (COOH) and a hydrogen atom (H)
• Additionally, each amino acid contains a variable side chain (R) which gives the amino acid specific chemical properties

There are 20 different amino acids which are naturally occurring and genetically incorporated by all living organisms (i.e. universal)

• Over 500 modified variants of amino acids are found in proteins, but only 20 amino acids are universally encoded by DNA sequences

Each amino acid has a distinctive side chain (variable group) with specific chemical properties that will cause the protein to fold and function differently according to the positions of the amino acids within the protein

• E.g. Membrane channel proteins have a hydrophobic exterior (face fatty acids) and a hydrophilic inner pore (allows ion passage) 

The 20 Universal Amino Acids (click on the diagram to swap between chemical and molecular representations)

Polypeptides

Amino acids can be covalently joined together in a condensation reaction to form a peptide bond (water is produced as a by-product)

• Two amino acids combine to form a dipeptide, and long chains of covalently bonded amino acids are called polypeptides
• Polypeptide chains can be broken down into reusable amino acids via hydrolysis reactions (requires water to reverse the process)

Peptide bonds are formed between the amine group (NH₂) and carboxylic acid group (COOH) of adjacent amino acids

• The amine group loses a hydrogen (H) and the carboxylic acid loses a hydroxyl (OH): these combine to form water (H₂O)

Levels of Protein Structure

Polypeptide chains coil and fold due to the properties of their amino acids to achieve different levels of protein structure

• Each level of protein structure builds on the previous level to determine the overall structural organisation of the protein

Primary (1º) Structure:

• The first level of structural organisation in a protein is the order of amino acids which comprise the polypeptide chain
• The primary structure is formed by covalent peptide bonds between the amine and carboxyl groups of adjacent amino acids
• Primary structure controls all subsequent levels because it determines the sequence of the R groups in the polypeptide chain

Secondary (2º) Structure

• The secondary structure is the way a polypeptide folds in a repeating arrangement to form α-helices and β-pleated sheets
• This folding is a result of hydrogen bonding between the amine and carboxyl groups of non-adjacent amino acids
• The α-helices increase the tensile strength of the polypeptide, while β-pleated sheets increase the mechanical stability
• Sequences that do not form either an alpha helix or beta-pleated sheet will exist as a random coil
• In pictures, alpha helices are represented as spirals and beta-pleated sheets are represented as arrows

Tertiary (3º) Structure

• The tertiary structure is the way the polypeptide chain coils and turns to form a complex molecular shape (i.e. the 3D shape)
• It is caused by interactions between R groups; including H-bonds, disulfide bridges, ionic bonds and hydrophobic interactions
• Relative amino acid positions are important (e.g. non-polar amino acids usually avoid exposure to aqueous solutions)
• Tertiary structure may be important for the function of the protein (e.g. specificity of active site in enzymes)

Quaternary (4º) Structure

Certain proteins may possess a fourth level of structural organisation called a quaternary structure

• Quaternary structures are found in proteins that consist of more than one polypeptide chain linked together 
• Alternatively, proteins may have a quaternary structure if they include inorganic prosthetic groups within their structure
• Not all proteins will have a quaternary structure – many proteins will only consist of a single polypeptide chain

An example of a protein with a quaternary structure is haemoglobin (an oxygen carrying molecule in red blood cells)

• Haemoglobin is composed of four polypeptide chains (two alpha chains and two beta chains)
• It is also composed of iron-containing haeme groups (prosthetic groups that are responsible for binding oxygen)

Denaturation

Because the way a protein folds determines its function, any change or abrogation to the tertiary structure will alter its activity

Denaturation is a structural change in a protein that results in the loss (usually permanent) of its biological properties

• Denaturation of proteins can usually be caused by two key conditions – temperature and pH
  

Temperature

• High levels of thermal energy may disrupt the hydrogen bonds that hold the protein together
• As these bonds are broken, the protein will begin to unfold and lose its capacity to function as intended
• Temperatures at which proteins denature may vary, but most human proteins function optimally at body temperature (~37ºC)
  
  

pH

• Amino acids are zwitterions, neutral molecules possessing both negatively (COO^–) and positively (NH₃⁺) charged regions 
• Changing the pH will alter the charge of the protein, which in turn will alter protein solubility and overall shape
• All proteins have an optimal pH which is dependent on the environment in which it functions (e.g. stomach = low pH)

Functions of Proteins

Proteins are a very diverse class of compounds and may serve a number of different roles within a cell, including:

• Structure – e.g. collagen, spider silk
• Hormones – e.g. insulin, glucagon
• Immunity – e.g. immunoglobulins
• Transport – e.g. haemoglobin
• Sensation – e.g. rhodopsin
• Movement – e.g. actin, myosin
• Enzymes – e.g. Rubisco, catalase

Proteomes

The proteome is the totality of proteins expressed within a cell, tissue or organism at a certain time

• The proteome of any given individual will be unique, as protein expression patterns are determined by an individual’s genes

The proteome will typically be significantly larger than the number of genes in an individual due to a number of factors:

• Gene sequences may be alternatively spliced following transcription to generate multiple protein variants from a single gene
• Proteins may be modified (e.g. glycosylated, phosphorylated, etc.) following translation to promote further variations