RH

BICH 410 Ch 7 Protein Function 1-6-22

Chapter 7: Protein Function - Hemoglobin and Myoglobin

Part 1: Structure and Function of Influenza Hemagglutinin

Overview of Influenza Virus

  • Influenza virus infects cells via endocytosis.

  • Membrane fusion triggered by low pH of the endosome.

Hemagglutinin Function

  • Functions as a spring-loaded mechanism that undergoes conformational changes.

  • Pre-fusion and post-fusion structures (HA, fused membrane, and fusion peptide).

  • Protonation releases the fusion peptide, leading to membrane fusion.

Part 2: Myoglobin and Hemoglobin

Myoglobin

  • Single heme prosthetic group contributes to its hyperbolic O2 binding curve.

  • Higher affinity for oxygen than hemoglobin at all oxygen pressures.

Hemoglobin

  • Exists in deoxy (T) and oxy (R) conformations, affecting O2 binding affinity.

  • Binding of O2 induces conformational changes, promoting cooperative binding and yielding a sigmoidal O2 binding curve.

  • Influences of Bohr effect and BPG on hemoglobin's oxygen binding affinity.

Structural Overview

  • Myoglobin: Monomeric with 153 amino acids and a molecular weight of 17,200.

  • Hemoglobin: Tetrameric structure with two alpha and two beta chains (141 residues each for alpha, 146 for beta).

Cooperative and Allosteric Binding

  • Oxygenation alters the structure of hemoglobin leading to cooperativity in oxygen binding.

  • Bohr Effect explains how CO2 and H+ influence oxygen release in tissues and binding in lungs.

  • 2,3-Bisphosphoglycerate (2,3-BPG) acts as an allosteric effector of hemoglobin, affecting its oxygen binding curve.

Pathological Conditions

Sickle-Cell Anemia

  • Caused by a mutation in the β-chains of hemoglobin (Glu to Val).

  • Results in crescent-shaped red blood cells that impair circulation.

  • Sickle-shaped cells derive from polymerization of Hb S which can lead to severe tissue damage.

Treatment Approaches

  • Hydroxyurea promotes production of fetal hemoglobin (Hb F) which does not sickle cells.

Summary of Key Points

  1. Myoglobin is for oxygen storage, while hemoglobin is for transport, regulated allosterically.

  2. Fetal hemoglobin has higher oxygen affinity due to lack of BPG binding.

  3. Sickle-cell anemia illustrates the effects of mutations in hemoglobin structure, linked to malaria resistance.