describe the structure of a molecule of haemoglobin as an example of a globular protein, including the formation of its quaternary structure from two alpha (α) chains (α–globin), two beta (β) chains (β–globin) and a haem group
Proteins – Haemoglobin as a Model Globular Protein
Learning Objective
Describe the structure of a molecule of haemoglobin, illustrating how its quaternary structure is assembled from two α‑chains (α‑globin), two β‑chains (β‑globin) and a haem group.
Key Structural Levels of Proteins
Primary structure: linear sequence of amino‑acid residues linked by peptide bonds.
Tertiary structure: three‑dimensional shape of a single polypeptide chain, formed by interactions among side‑chains (hydrophobic, ionic, disulphide, etc.).
Quaternary structure: association of two or more polypeptide subunits into a functional protein complex.
Overall Architecture of Haemoglobin
Haemoglobin (Hb) is a tetrameric globular protein found in red blood cells. Its quaternary structure consists of:
Two α‑globin polypeptide chains (≈141 amino acids each).
Two β‑globin polypeptide chains (≈146 amino acids each).
Four prosthetic haem groups, each covalently attached to a histidine residue in the interior of a globin subunit.
Suggested diagram: A schematic of the haemoglobin tetramer showing the arrangement of α‑ and β‑chains around the four haem groups.
Composition of a Single Subunit
Each globin subunit (α or β) folds into a characteristic globin fold:
Eight α‑helices (named A–H) arranged in a roughly spherical shape.
The haem group is nestled in a pocket formed mainly by helices E and F.
Haem Group
The haem prosthetic group is a planar porphyrin ring with an iron ion at its centre, capable of binding one molecule of O₂.
Its simplified chemical representation is:
\$\text{Fe}^{2+}\text{(porphyrin ring)}\$
and its molecular formula can be approximated as \$C{34}H{32}N{4}O{4}Fe\$.
Quaternary Assembly
The four subunits associate through non‑covalent interactions (hydrogen bonds, salt bridges, hydrophobic contacts). The arrangement is often described as a “dimer of dimers”:
α₁β₁ forms one dimer.
α₂β₂ forms the second dimer.
The two dimers are linked to give the functional tetramer α₂β₂.
Table: Subunit and Haem Content of Human Haemoglobin
Component
Number per Hb molecule
Key Features
α‑globin chain
2
141 aa; binds one haem; contains proximal His (F8) and distal His (E7).
β‑globin chain
2
146 aa; similar haem pocket; differs in surface residues affecting allosteric regulation.
Haem group
4
Protoporphyrin IX with Fe²⁺; each binds one O₂ molecule.
Functional Implications of the Quaternary Structure
The tetrameric arrangement allows cooperative binding of oxygen – the binding of O₂ to one haem increases the affinity of the remaining haem groups. This is explained by the transition between the “tense” (T) and “relaxed” (R) conformations of the protein.
Summary
Haemoglobin exemplifies a globular protein whose biological activity depends on a well‑ordered hierarchy of structure:
Primary sequence of α‑ and β‑chains.
Secondary α‑helices forming the globin fold.
Tertiary folding that creates a haem‑binding pocket.
Quaternary assembly of two α‑ and two β‑chains with four haem groups, enabling efficient oxygen transport.