Explain quaternary structure of haemoglobin. (IFS 2021, 8 Marks)

Introduction

Haemoglobin is a protein found in red blood cells that is responsible for carrying oxygen from the lungs to the rest of the body. It is composed of four subunits, each containing a heme group that binds to oxygen. The quaternary structure of haemoglobin refers to the arrangement of these subunits and how they interact with each other to form the functional protein.

Quaternary Structure of Hemoglobin

• Definition of Quaternary Structure:
  
  • The quaternary structure of a protein refers to the spatial arrangement and interactions between multiple polypeptide chains (subunits) that form the complete functional protein.
  • In the case of haemoglobin, the quaternary structure involves the interaction between four subunits: two alpha (α) chains and two beta (β) chains.
• Subunit Composition:
  
  • Alpha Chains: Hemoglobin has two alpha (α) globin chains, each with 141 amino acid residues.
  • Beta Chains: There are two beta (β) globin chains, each with 146 amino acid residues.
  • Each subunit contains a heme group that binds oxygen.
• Subunit Interactions:
  
  • The α and β chains interact through non-covalent bonds, such as hydrogen bonds, hydrophobic interactions, and ionic bonds.
  • The four subunits are arranged in a symmetrical structure, where each subunit is able to bind oxygen molecules, with cooperative binding being a critical feature.
• Cooperative Binding of Oxygen:
  
  • Hemoglobin's quaternary structure facilitates the cooperative binding of oxygen. This means that when one subunit binds an oxygen molecule, it induces a conformational change in the other subunits, increasing their affinity for oxygen.
  • This cooperativity results in a sigmoidal (S-shaped) oxygen dissociation curve, which is efficient for oxygen uptake in the lungs and release in tissues.
• Tense (T) and Relaxed (R) States:
  
  • Haemoglobin exists in two primary conformational states: T (tense) and R (relaxed).
  • T-State (Tense): In this state, the affinity for oxygen is low, and oxygen is less likely to bind.
  • R-State (Relaxed): In this state, the affinity for oxygen is high, allowing for easier oxygen binding.
  • The transition between these states is driven by the binding of oxygen to the subunits.
• Allosteric Regulation: The quaternary structure of hemoglobin also allows for allosteric regulation. The binding of oxygen affects the binding of oxygen to other subunits (positive cooperativity), and the binding of other molecules, such as carbon dioxide (CO2) and protons (H+), can decrease hemoglobin's affinity for oxygen (negative cooperativity). This is known as the Bohr effect.

Conclusion

The quaternary structure of haemoglobin plays a crucial role in its function as an oxygen-carrying protein. The arrangement of four subunits and their interaction with each other allows for efficient binding and transport of oxygen throughout the body.