Structure-Function Relationship in Proteins

Structure-Function Relationship in Specific Proteins

• Globular proteins exhibit a compact, rounded shape, making them water-soluble. These proteins are crucial in diverse biological processes, including enzyme activity, transport, and regulation. Examples include hemoglobin and myoglobin.
• Fibrous proteins are insoluble in water. Their hydrophobic amino acid residues concentrate on the interior and surface, lending strength and flexibility to their structures. They form elaborate supramolecular complexes. Examples include collagen, myosin, and actin fibers.

Globular Proteins: Hemoglobin and Myoglobin

• Hemoglobin is an oligomeric protein (quaternary structure) whose function is to transport gases in the blood. It contains 4 polypeptide chains and 4 heme prosthetic groups, including 2 alpha and 2 beta subunits. Subunits are arranged symmetrically with non-covalent interactions.
• Myoglobin is a monomeric protein. It stores oxygen within muscle tissue for times of intense respiration. Myoglobin's role is different from hemoglobin as it releases oxygen upon lower oxygen pressures. Both hemoglobin and myoglobin are conjugated proteins with an associated heme prosthetic group that contains iron in the ferrous state (Fe2+).

Globular Proteins: Heme Group Structure

• The heme group's complex organic ring structure is porphyrin.
• The iron atom in heme has 6 coordination bonds: 4 in the plane of the porphyrin ring system, and 2 perpendicular to it.
• The proximal histidine residue coordinates with the iron (perpendicular direction); the distal histidine residue is near the iron (but not directly bonded), and is important to regulate oxygen binding and preventing carbon monoxide binding.
• Iron is protected from oxidation within a hydrophobic pocket of the apoprotein. This pocket also prevents CO from binding.

Agents Affecting Oxygen Binding in Hemoglobin

• Protons (H⁺) and carbon dioxide (CO2), waste products from cellular respiration, lower hemoglobin's affinity for oxygen as both molecules are released to tissues.
• 2,3-bisphosphoglycerate (BPG) is an important physiological adaptation to high altitude. Decreased affinity for oxygen, increasing oxygen release to tissues.

Allosteric Properties

• Allosteric proteins, like hemoglobin, typically have multiple subunits with multiple ligand-binding sites, enabling a change in conformation when a ligand binds at one site. This affects ligand binding at another site.
• The binding of the first oxygen molecule to hemoglobin shifts the structure leading to enhanced oxygen binding to the other subunits in the molecule. This facilitates an effective transport mechanism of oxygen.

Fibrous Proteins: Collagen

• Collagen is insoluble in water, comprised of primarily glycine, proline, and hydroxyproline amino acids. Its secondary structure is a left-handed helix.
• Its triple helix of polypeptide chains forms tropocollagen. Tropocollagen molecules aggregate to form collagen fibers that provide strength to various connective tissues, such as tendons, cartilage, bone, and the cornea of the eye.
• Cross-linking of collagen fibers, facilitated by covalent bonds, increases with age, making tissues more rigid.

Fibrous Proteins: Myosin

• Myosin is a six-subunit protein containing two heavy chains and two light chains.
• Its carboxyl terminus is associated with a region of extended alpha-helix structure and a left-handed supercoiled helix. A globular domain contains the site where ATP is hydrolyzed.
• The light chains are associated with the globular domains. Myosin is a key component in muscle contraction, thick filaments, which are composed of multiple myosin molecules.

Fibrous Proteins: Actin

• Actin is a monomeric (G-actin) protein that polymerizes into a filamentous (F-actin) structure, which is right-handed.
• Thin filaments are composed of F-actin, troponin, and tropomyosin. Each actin monomer tightly binds to a myosin head group, which is a key element in muscle contraction and regulation.

Fibrous Proteins: Collagen Types

• Different collagen types (at least 27) have different tissue distributions and functions based on their structural differences, particularly the degree and presence of covalent cross-links.
• Various collagen types support the structure and function in numerous tissues, ensuring flexibility, structure, and resistance to stress.

Diseases Associated with Collagen

• Osteogenesis imperfecta is a genetically-based disorder characterized by brittle bones prone to fractures.
• Scurvy, caused by a lack of vitamin C, affects the proper formation of hydroxyproline in collagen, affecting the stability of the triple helix structure and leading to a variety of connective tissue disorders.