2.2.11 Protein: Structure

• There are four levels of structure in proteins, three are related to a single polypeptide chain and the fourth level relates to a protein that has two or more polypeptide chains
• Polypeptide or protein molecules can have anywhere from 3 amino acids (Glutathione) to more than 34,000 amino acids (Titan) bonded together in chains

Primary structure

• The sequence of amino acids bonded by covalent peptide bonds is the primary structure of a protein
• The DNA of a cell determines the primary structure of a protein by instructing the cell to add certain amino acids in specific quantities in a certain sequence. This affects the shape and therefore the function of the protein
• The primary structure is specific for each protein (one alteration in the sequence of amino acids can affect the function of the protein)

The primary structure of a protein. The three-letter abbreviations indicate the specific amino acid (there are 20 commonly found in cells of living organisms).

Secondary structure

• The secondary structure of a protein occurs when the weak negatively charged nitrogen and oxygen atoms interact with the weak positively charged hydrogen atoms to form hydrogen bonds
• There are two shapes that can form within proteins due to the hydrogen bonds:
  • α-helix
  • β-pleated sheet

• The α-helix shape occurs when the hydrogen bonds form between every fourth peptide bond (between the oxygen of the carboxyl group and the hydrogen of the amine group)
• The β-pleated sheet shape forms when the protein folds so that two parts of the polypeptide chain are parallel to each other enabling hydrogen bonds to form between parallel peptide bonds
• Most fibrous proteins have secondary structures (e.g. collagen and keratin)
• The secondary structure only relates to hydrogen bonds forming between the amino group and the carboxyl group (the ‘protein backbone’)
• The hydrogen bonds can be broken by high temperatures and pH changes

The secondary structure of a protein with the α-helix and β-pleated sheet shapes highlighted. The magnified regions illustrate how the hydrogen bonds form between the peptide bonds.

Tertiary structure

• Further conformational change of the secondary structure leads to additional bonds forming between the R groups (side chains)
• The additional bonds are:
  • Hydrogen (these are between R groups)
  • Disulphide (only occurs between cysteine amino acids)
  • Ionic (occurs between charged R groups)
  • Weak hydrophobic interactions (between non-polar R groups)

• This structure is common in globular proteins

The tertiary structure of a protein with hydrogen bonds, ionic bonds, disulphide bonds and hydrophobic interactions formed between the R groups of the amino acids.

Disulphide

• Disulphide bonds are strong covalent bonds that form between two cysteine R groups (as this is the only amino acid with a sulphur atom)
• These bonds are the strongest within a protein but occur less frequently, and help stabilise the proteins
• These are also known as disulphide bridges
• Disulphide bonds can be broken by oxidation
• This type of bond is common in proteins secreted from cells eg. insulin

Ionic

• Ionic bonds form between positively charged (amine group -NH₃⁺) and negatively charged (carboxylic acid -COO^-) R groups
• Ionic bonds are stronger than hydrogen bonds but they are not common
• These bonds are broken by pH changes

Hydrogen

• Hydrogen bonds form between strongly polar R groups. These are the weakest bonds that form but the most common as they form between a wide variety of R groups

Hydrophobic interactions

• Hydrophobic interactions form between the non-polar (hydrophobic) R groups within the interior of proteins

Tertiary structure determines function

• A polypeptide chain will fold differently due to the interactions (and hence the bonds that form) between R groups
• Each of the twenty amino acids that make up proteins has a unique R group and therefore many different interactions can occur creating a vast range of protein configurations and therefore functions

The interactions that occur between the R groups of amino acids determines the shape and function of a protein. These interactions are found within tertiary structures of proteins.

Quaternary structure

• Quarternary structure exists in proteins that have more than one polypeptide chain working together as a functional macromolecule, for example, haemoglobin
• Each polypeptide chain in the quaternary structure is referred to as a subunit of the protein

The quaternary structure of a protein. This is an example of haemoglobin which contains four subunits (polypeptide chains) working together to carry oxygen.

Summary of Bonds in Proteins Table