Structure-Function of Globular Proteins

Structure-Function Relationship in Specific Proteins

• Globular proteins, such as hemoglobin and myoglobin, have a compact, roughly spherical shape.
• Globular proteins are water-soluble, readily dissolving in blood.
• Globular proteins have diverse functions, including acting as enzymes, transporting substances, and regulating processes.
• Examples of globular proteins are enzymes, transport proteins, motor proteins, regulatory proteins, and immunoglobulins.
• Globular proteins have a size range from 2000Å x 5Å (B conformation) to 900Å x 11Å (a helix).

Myoglobin and Hemoglobin

• Myoglobin is a heme protein found in muscle tissue.
• Its function is to store oxygen and supply for intense respiration.
• Myoglobin has a tertiary structure.
• Hemoglobin is a heme protein found in red blood cells (erythrocytes).
• Its function is to transport oxygen from the lungs to tissues and carbon dioxide from tissues to the lungs.
• Hemoglobin has a quaternary structure.
• Both myoglobin and hemoglobin have heme prosthetic groups that contain iron in its ferrous (Fe²⁺) state.

Heme Group Structure

• The heme group's complex organic ring structure is a protoporphyrin.
• Iron at the center of the heme group forms six coordination bonds.
• Four bonds are in the same plane as the porphyrin ring
• Two bonds are perpendicular to the plane of the porphyrin ring.

Globular Proteins - Important Residues

• The heme group is located within a hydrophobic pocket in the apoprotein.
• This protects the iron from oxidation.
• The pocket also prevents carbon monoxide from binding to the heme group.
• In both myoglobin and hemoglobin, specific amino acid residues are crucial for oxygen binding.

Hemoglobin (Continued)

• Hemoglobin is an oligomeric protein with a quaternary structure.
• It consists of four polypeptide chains (2 α subunits and 2 β subunits).
• Each subunit has a bound heme prosthetic group.
• Subunits are arranged in pairs.
• Their arrangement in the protein relies on noncovalent interactions.

Allosteric Interactions (Hemoglobin)

• Hemoglobin is an allosteric protein, meaning interactions at one site influence binding at another.
• Oxygen binding to one subunit facilitates oxygen binding to adjacent subunits.
• Hemoglobin exhibits two main conformational states (T-state and R-state).
• The binding of oxygen causes a conformational shift (T → R).
• The change in shape increases oxygen binding affinity in hemoglobin.

Factors Affecting Oxygen Binding (Hemoglobin)

• The concentration of protons (H⁺) and carbon dioxide (CO₂) in peripheral tissues affects hemoglobin's oxygen affinity.
• High H⁺ and CO₂ levels reduce oxygen affinity.
• This allows oxygen release to the tissues as needed.
• 2,3-bisphosphoglycerate (BPG) is another factor influencing oxygen affinity.
• Higher BPG concentration decreases oxygen affinity in hemoglobin.

Fibrous Proteins (General Description)

• Fibrous proteins are insoluble in water due to their high concentration of hydrophobic amino acids on their surfaces.
• They play important structural functions, often providing strength and flexibility to tissues.
• They form complex supramolecular structures with similar polypeptide chains packed together.
• Common examples include collagen, myosin, and actin.

Collagen

• Collagen is an important structural fibrous protein.
• It provides strength to connective tissues like tendons, cartilage, and bone.
• Collagen has a highly organized, repetitive amino acid sequence (Gly-X-Y).
• Contains large amounts of Glycine, Proline, and Hydroxyproline amino acids.
• These particular amino acids are important components of the left-handed coiled structure in collagen.
• Collagen fibers are also stabilised by cross-links, which are covalent bonds resulting in differing degrees of flexibility or rigidity.

Myosin

• Myosin is a fibrous protein that is a component in muscle cells.
• It contains multiple subunits, including 2 heavy chains and 2 light chains.
• The carboxyl terminus of the polypeptide chains forms a long tail, with the amino terminus forming a head.
• The head forms cross bridges with actin in muscle contraction.

Actin

• Actin is a fibrous protein that also plays a role in muscle contraction.
• It's a component of the thin filaments in muscle.
• Actin is composed of G-actin monomers in a right-handed polymerized structure called F-actin.
• Actin has a high affinity for G-actin monomers with specific binding sites for myosin.