Protein Structure — Primary, Secondary and Tertiary

A polypeptide chain is not a functional protein until it has folded into a precise three-dimensional shape. Protein structure is described at four hierarchical levels — primary, secondary, tertiary and quaternary. This lesson examines the first three, showing how amino acid sequence gives rise to function. It covers OCR specification point 2.1.2 (d)(iii).

1. Overview of the Four Levels

graph TD
  A[Primary structure<br/>Sequence of amino acids<br/>Peptide bonds only] --> B[Secondary structure<br/>α-helix and β-pleated sheet<br/>Hydrogen bonds between backbone]
  B --> C[Tertiary structure<br/>Overall 3D fold of one polypeptide<br/>R group interactions]
  C --> D[Quaternary structure<br/>Two or more polypeptide subunits<br/>Same R group interactions]

Key Principle: Each higher level of structure depends on the lower levels. The sequence of amino acids (primary structure) ultimately determines everything else about how a protein folds and functions.

2. Primary Structure

The primary structure of a protein is the specific sequence of amino acids in the polypeptide chain, held together by peptide bonds.

Features of primary structure:

Unique to each protein — determined by the order of codons in the gene.
Written from N-terminus (left) to C-terminus (right) using three-letter or one-letter abbreviations (e.g., Met-Val-Leu-Ser-Pro... or MVLSP...).
The only bond involved at this level is the peptide bond — no folding or interactions yet.
Even a single amino acid change can dramatically alter function — sickle cell anaemia results from a single glutamic acid (Glu) → valine (Val) substitution at position 6 of the β-chain of haemoglobin.

3. Secondary Structure

Secondary structure refers to the regular, repeating folding patterns that arise from hydrogen bonding between atoms in the polypeptide backbone — specifically between the carbonyl oxygen (C=O) of one peptide group and the amide hydrogen (N–H) of another. R groups are not involved at this level.

There are two main secondary structures.

3.1 The α-Helix

An α-helix is a right-handed helical coil, resembling a spiral staircase.

Each turn of the helix contains 3.6 amino acids.
The pitch (vertical distance per turn) is 0.54 nm.
Hydrogen bonds form between the C=O of one amino acid and the N–H of the amino acid four residues further along the chain (i and i + 4).
R groups project outward from the helix.
The helix is held together entirely by hydrogen bonds along the backbone.

   .C=O ......H-N.
          |
        (helix)
          |
   .C=O ......H-N.

Proteins rich in α-helices include keratin (hair, wool, nails) and myoglobin.

3.2 The β-Pleated Sheet

A β-pleated sheet consists of polypeptide chains (called β-strands) running either in the same direction (parallel) or in opposite directions (antiparallel), laid side by side and connected by hydrogen bonds.

The strands zigzag to form a pleated, sheet-like structure.
Hydrogen bonds form between strands — C=O of one strand to N–H of the next.
R groups alternate above and below the plane of the sheet.
Sheets may be flat or twisted.

Strand 1:  —N–H  C=O  N–H  C=O  N–H  C=O—
                :     :     :     :     :
                :     :     :     :     :
Strand 2:  —C=O  N–H  C=O  N–H  C=O  N–H—

Proteins rich in β-pleated sheets include silk fibroin and amyloid deposits.

3.3 Other Secondary Features

β-turns and loops — short regions connecting α-helices and β-strands, allowing the chain to reverse direction.
Random coil — regions with no regular pattern, but still precisely folded.

4. Tertiary Structure

Tertiary structure is the overall three-dimensional shape of a single polypeptide chain, produced by interactions between the R groups (side chains). Tertiary structure gives the protein its functional shape, including the active site of an enzyme.

Tertiary structure arises from five types of R group interactions:

4.1 Hydrogen Bonds

Formed between polar R groups (e.g., serine, threonine, asparagine, glutamine, tyrosine). Individually weak but collectively important.

Lesson 9: Protein Structure — Primary, Secondary and Tertiary