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Lesson 4 of 6 / Biological molecules

From amino acids to a folded protein

How does a sequence produce a specific three-dimensional shape?

In this lesson: Explain amino acids, peptide bonds and four levels of protein structure.

About 7 min

The key ideaAmino-acid sequence constrains folding; different interactions stabilise secondary, tertiary and quaternary structures.

Explore the idea

Move between levels of structure

A particular sequence

Peptide bonds join amino acids in a particular order. Different colours represent different R groups.

Inspect an amino acid and its peptide linkCHR groupNH2COOHFour groups on the central carbon

Condensation between a carboxyl group and an amino group forms the backbone link -CO-NH- and releases water. The R groups remain side chains. This conventional uncharged structural formula identifies the groups; their ionisation depends on pH.

Hydrogen and ionic interactions and hydrophobic clustering help determine folded shape. A disulfide bridge is a covalent S-S link between suitable cysteine side chains; it is not a peptide bond.

Explanation

An amino acid has an amino group, a carboxyl group, hydrogen and a variable R group attached to a central carbon. R groups differ in properties such as charge and polarity. Condensation between amino and carboxyl groups forms a peptide bond; hydrolysis reverses the join. The amino-acid sequence is the primary structure.

Secondary structure is local folding of the backbone into arrangements such as alpha helices and beta-pleated sheets. Hydrogen bonds form between backbone carbonyl and amino groups. These are not new peptide bonds and do not require a second polypeptide.

Tertiary structure is the overall three-dimensional conformation of one polypeptide. Hydrogen bonds, ionic interactions, covalent disulfide bridges between suitable cysteine residues, and hydrophobic interactions involving non-polar R groups help stabilise it. Hydrophobic residues often cluster away from surrounding water.

Quaternary structure describes the association of two or more polypeptide subunits into a functional protein. Not every protein has this level. The positions of R groups create binding sites and surfaces with particular shapes and chemical properties; sequence changes can therefore alter function without changing the total length of a protein.

Step by step
  1. 1

    Start with the sequence

    Identify the covalent peptide backbone.

  2. 2

    Separate local and overall folding

    Do not confuse a helix with the whole protein shape.

  3. 3

    Name appropriate interactions

    Disulfide bridges are covalent; hydrogen and ionic interactions are different.

Worked example

Work through the evidence

A functional protein contains four folded polypeptide chains. What levels of structure are present?

One way to explain it

Each chain has primary, secondary and tertiary structure. Their association produces quaternary structure.

Why this answer works
  • A polypeptide chain is not the same as an amino-acid monomer.
  • Quaternary structure concerns subunits, not a fourth type of bond.
Is this true? "Every protein must have all four levels."

A protein with one polypeptide may have no quaternary structure.

Try a question

Which stabilises a typical alpha helix?
You can return to this lesson any time.