Levels of Protein Structure (DP IB Biology)

Primary Structure

Levels of Protein Structure

• Proteins are relatively large, complex molecules that contain one or more chains of amino acids known as polypeptides

• The three-dimensional arrangement of polypeptide chains dictates a protein's structure and function

• There are four levels of structure in proteins

  • Three levels are structural aspects of a single polypeptide chain

  • The fourth level relates to a protein that has more than one polypeptide chain

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 specific, ordered sequence

• This affects the shape, and therefore the function, of the protein

• The primary structure is specific for each protein

• Some mutations can lead to the incorrect amino acid being incorporated into the polypeptide chain which can affect the function of the protein

Primary structure diagram

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

• Secondary structure is the formation of complex shapes within the polypeptide chain

• Secondary structure of a protein occurs due to weak hydrogen bonds

  • Hydrogen bonds form between carboxyl (C=O) groups and amino (N-H) groups

  • The bonds usually form between non-adjacent amino acids resulting in a change in shape of the linear polypeptide chain

• There are two shapes that can form within proteins due to the hydrogen bonds:

  • Alpha-helix (or α-helix)

  • Beta-pleated sheet (or β-pleated sheet)

Protein secondary structure diagram

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

Tertiary Structure: Chemical Bonds

Polar and non-polar amino acids are relevant to the bonds formed between R groups

• Tertiary structure refers to how the polypeptide chain folds to form a complex, three-dimensional shape

• Tertiary structure gives proteins a very specific shape that is important for function

  • Such as receptor sites on cell membranes and active sites in enzymes

• Folding results from interactions between R groups (side chains) of the amino acids and the surrounding environment

• A number of different interactions between R-groups contribute to the tertiary structure

  • Hydrogen bonds form between polar R-groups

  • Hydrophobic interactions form between the R-groups of non-polar amino acids within the interior of proteins to avoid contact with water

  • Covalent bonds form between the R-groups of cysteine amino acids to form disulfide bridges

  • Ionic bonds form between positively and negatively charged R-groups

    • R-groups can become positively or negatively charged by the dissociation or binding of hydrogen ions

Protein tertiary structure diagram

The interactions that occur between the R groups of amino acids determine the tertiary structure and function of a protein

Summary of bonds in proteins table

Tertiary Structure: Amino Acids

• Amino acids are either polar or non-polar depending on their R-groups

• Proteins composed of non-polar amino acids are less soluble in aqueous solutions such as the cytoplasm 

• Therefore these proteins are generally used for structural purposes and are stationary so are not required to be soluble

  • They are found in the centre of a protein helping to stabilise the structure

  • They can help form the active site of lipase enzymes to allow interaction with lipid substrates

  • They tend to be localised on the surface of a cell so are in contact with the membrane, such as glycoproteins

• Proteins with polar amino acids are soluble and are found in a variety of places within the cell

  • They can be found on the surface of a membrane as they are capable of interacting with water molecules

  • They can line interior pores within the membrane, which creates hydrophilic channels for transport of polar molecules into and out of a cell

  • They are found on the outside of enzymes so that enzymes are soluble in aqueous environments

Quaternary Structure

Quaternary structure

• Large proteins often consist of multiple polypeptide chains functioning together as a larger biologically active macromolecule

  • Each polypeptide chain is referred to as a subunit of the protein

• Many proteins also contain non-polypeptide components (prosthetic groups) and are classed as conjugated proteins

• Quaternary structure refers to how polypeptides and other components are arranged

  • This relates closely to function

  • Proteins with only one polypeptide chain do not have a quaternary structure

• Haemoglobin is a conjugated protein, having quaternary structure, as it consists of multiple polypeptide chains (making four subunits) each with a prosthetic group

  • There are two pairs of identical polypeptide chains (α–globins and β–globins)

  • Each subunit has a prosthetic haem group which contains an iron ion (Fe²⁺)

Haemoglobin structure diagram

The quaternary structure of haemoglobin.
Four subunits (polypeptide chains) and prosthetic haem groups work together to carry oxygen.

• Insulin and collagen are non-conjugated proteins meaning they have no other non-protein components 

• Insulin:

  • Consists of two chains of amino acids, one being 21 amino acids long, the other 30 amino acids in length; the chains are joined by disulfide bridges

  • It forms two quaternary different structures called dimers and hexamers which act as storage molecules of insulin

• Collagen:

  • It is a fibrous protein consisting of three polypeptide chains wound together in a helix shape

  • It is the arrangement of the helix shape that gives collagen its quaternary structure

NOS: Technology allows imaging of structures that would be impossible to observe with the unaided senses. For example, cryogenic electron microscopy has allowed imaging of single-protein molecules and their interactions with other molecules

• The technique of cryogenic electron microscopy (cryo-EM) involves rapid freezing of protein solutions and then exposing them to many electrons to produce a microscopic image

• The images can be used to recreate 3D shape or structure of proteins allowing us to visualise how they interact with other molecules within a cellular environment

• Cryo-EM has different applications depending on the type of protein or molecule being studied so observations can be extremely purposeful and exact

• Until recently, proteins had to be crystallised to reconstruct and visualize them with X-ray crystallography which posed many problems such as:

  • Crystallisation is time consuming and can only work on single purified protein

  • Some proteins do not crystallise

  • The structure has to be visualised outside of the cellular environment which removes contextual information and interactions with other molecules