Principles of Protein Structure - H. Schulz 1982

Covalent Protein Structure
Chain Ensembles
Three Main Physiological Types of Protein Molecules

The types of bonds between functional domains (covalent or non-covalent), as well as their absence, can be correlated with the physiological environment in which a protein resides. Most intracellular Proteins are oligomeric; Blood Plasma Proteins are large monomers consisting of several functional domains; whereas proteins functioning outside the Organism* are small monomers. Let us explore the rationale behind this distribution.

Extraepithelial proteins are small monomers. Outside the organism, The Fate of an individual molecule (such as a human digestive protein or Lysozyme) is highly uncertain. Therefore, it is advantageous to maximize the number of independent functional units produced from a given amount of protein material, which accounts for their small size. Furthermore, these proteins are monomeric because oligomers tend to dissociate upon dilution.

Blood Plasma proteins are large monomers. A key characteristic of specific plasma proteins is their ability to be retained within the blood plasma. Only proteins with molecular weights of approximately 60,000 or greater are sufficiently large to prevent them from readily leaking into the extravascular space, a fate typical of smaller molecules (around 20,000). In addition, smaller proteins are readily filtered, processed, and excreted by the Kidneys.

Large blood plasma proteins can exist as either oligomers or monomers. However, oligomers are prone to dissociation, and their subunits can be filtered through the same pathways as small monomers. This is illustrated by β₂-microglobulin (Fig. 4.2, b), a small soluble subunit of HL-A proteins (which associate with The surface of certain Blood Cells and various other cells). This subunit of an oligomeric protein is known to penetrate capillary walls; moreover, under certain conditions (such as cadmium poisoning), large amounts of microglobulin are excreted in the urine. Consequently, true plasma proteins must be large monomeric rather than oligomeric structures. A classic example is serum albumin (Fig. 7.2, b), constructed from a set of functional domains [76, 82] within a single polypeptide chain. Some plasma Polypeptides significantly increase their overall size through covalently attached carbohydrate residues.

* Epithelial surfaces serve as the boundary between the internal environment of animals and the external environment; for instance, the Contents of the gastrointestinal tract are considered part of the external environment.

Intracellular proteins are typically oligomeric. Let us now examine intracellular proteins, which predominantly exist as oligomers. Small monomeric proteins, such as adenylate kinase Isoenzymes ($M = 22,000$) [83, 84], are rare within cells. In this context, oligomers offer several advantages over large single polypeptide chains (Section 4.1). Unlike in blood plasma, oligomers function with high efficiency inside cells because The Cell membrane is impermeable even to small proteins, thereby ruling out the loss of oligomers through subunit dissociation.

The formation of oligomers lowers the osmotic pressure within the intracellular space. In addition, the surface-to-volume ratio is smaller for an oligomer than for a monomer. Consequently, an oligomer binds fewer Water molecules and contributes less to intracellular viscosity. Finally, Oligomeric Proteins generally exhibit cooperativity and are tightly regulated by effectors. A well-known example of the physiological optimization of these properties is mammalian erythrocyte tetrameric Hemoglobin [85]. However, such properties are equally essential for less specialized cells containing A wide variety of proteins.