IB Biology Topic B1.2.9: Dependence of Tertiary Structure on Functional Groups Notes

Tertiary Structure: How R-Group Interactions Shape Protein Folding

1. The tertiary structure of a protein is the complete three-dimensional shape of a single folded polypeptide chain.
   1. Secondary structure comes from hydrogen bonds along the polypeptide backbone.
   2. Tertiary structure instead depends on interactions between the R-groups (side chains) of amino acids scattered along the sequence.
2. Four types of interaction stabilise tertiary structure: hydrogen bonds, ionic bonds, disulfide bonds, and hydrophobic interactions.
   1. Each operates differently, and together they hold the protein in a precise conformation.

Hydrogen Bonds Between Polar R-Groups

1. Hydrogen bonds form between polar R-groups, when a slightly positive hydrogen atom (for example in an -OH group) is attracted to an electronegative atom like the oxygen in a C=O group.
2. Each individual hydrogen bond is weak, but a protein contains hundreds of them.
   1. Collectively they provide a significant stabilising force.

Ionic Bonds Between Oppositely Charged R-Groups

1. Ionic bonds form between a positively charged R-group (like -NH₃⁺ on lysine) and a negatively charged R-group (like -COO⁻ on aspartate).
2. These electrostatic attractions are stronger than hydrogen bonds, but they are sensitive to pH.
   1. A shift in pH can change the charge on these groups, breaking the ionic bond and destabilising the protein's shape.

Disulfide Bonds: The Strongest Stabilisers

1. Disulfide bonds are covalent bonds (S-S) that form between the sulfur atoms of two cysteine residues.
2. Because they are covalent, they are far stronger than any of the non-covalent interactions and give the protein rigidity.
3. They are especially common in proteins that function outside cells, where conditions are harsher.
   1. Keratin in hair and antibodies in the blood both rely on disulfide bonds for structural stability.

Hydrophobic Interactions Drive the Overall Fold

1. Non-polar R-groups are repelled by water.
   1. In an aqueous environment they cluster together in the interior of the protein, away from the surrounding water.
   2. This is called the hydrophobic effect, and it is the main driving force behind protein folding.
2. Hydrophilic R-groups end up on the protein's surface, where they interact with water through hydrogen bonds.
   1. This arrangement minimises the protein's free energy and produces a stable, compact structure.

How the Four Interactions Work Together

1. No single type of interaction determines tertiary structure on its own.
   1. Hydrophobic interactions drive the overall fold by pushing non-polar residues inward.
   2. Hydrogen bonds and ionic bonds fine-tune the shape by stabilising specific regions of the chain.
   3. Disulfide bonds lock sections of the structure in place with covalent permanence.
2. The result is a precise three-dimensional shape that is essential for protein function.
   1. An enzyme's active site depends on the exact positioning of specific R-groups.
   2. That positioning is only possible because all four interactions work together to hold the chain in the correct conformation.

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