Mechanism of Protein Globule Formation
The process of protein folding into a compact globule is driven by the chemical properties of amino acids. Structure formation proceeds in two main directions:
- Formation of the hydrophobic core. Nonpolar (hydrophobic) amino acid side chains avoid contact with water. They aggregate inside the molecule via hydrophobic interactions and van der Waals forces, forming a dense interior center.
- Formation of the hydrophilic shell. Hydrophilic side chains (both ionized and non-ionized) remain on the protein surface. This outer surface interacts with the surrounding environment, ensuring good solubility of globular proteins in water.
Types of Bonds in Tertiary Structure
The three-dimensional shape is maintained by interactions between amino acid side chains. There are four primary types of these bonds:
- Ionic bonds — electrostatic attraction between groups with opposite charges.
- Hydrogen bonds — form between various uncharged hydrophilic groups.
- Hydrophobic interactions — clustering of nonpolar side chains within the interior of the globule.
- Disulfide bonds — strong covalent bridges formed by the oxidation and interaction of SH-groups from two cysteine residues. They provide additional stabilization for the structure of certain proteins.
Note: If hydrophilic residues are accidentally buried within the hydrophobic core, they can still interact with each other, forming hydrogen or ionic bonds.
Conformational Lability and Homeostasis
Ionic, hydrogen, and hydrophobic interactions are classified as weak bonds. Their energy only slightly exceeds the thermal motion of molecules. The overall protein conformation is maintained by a vast number of these weak contacts.
Atoms within the molecule are in constant motion, leading to the continuous breaking of some weak bonds and the formation of new ones, causing local shifts in chain segments. The ability of a protein to slightly alter its shape is called conformational lability.
The functional state of the molecule is called the native conformation. Under conditions of homeostasis (internal environment stability), natural lability does not prevent the protein from performing its functions. However, if the internal environment changes abruptly—such as fluctuations in proton, calcium ion, or glucose concentrations—the protein conformation is disrupted, leading to a loss of functional activity.
Structural Domains and Their Dynamics
Long polypeptide chains often do not form a single uniform sphere, but instead fold into several distinct, compact regions called domains. Each domain possesses its own independent tertiary structure, resembling a small, separate protein. The presence of domains significantly facilitates the correct folding of the entire complex molecule.
Domains are not static. When an enzyme's active site binds to a ligand, domains can change their relative positions. A classic example is the enzyme hexokinase, which catalyzes the transfer of a phosphate group from ATP to glucose. Its active site is located in a cleft between two domains. Following a "trap" mechanism, when hexokinase binds a glucose molecule, the surrounding domains close tightly together, securely trapping the substrate to carry out the chemical reaction.
Classification of Globular Proteins
Depending on the secondary structures present in the molecule, globular proteins are divided into four categories:
- First category includes proteins composed exclusively of $\alpha$-helices. Prominent examples are myoglobin and the $\beta$-chain of hemoglobin. A hallmark of these structures is the presence of exactly eight $\alpha$-helices in each molecule.
- Second category groups proteins that contain both $\alpha$-helices and $\beta$-sheets. This group includes triosephosphate isomerase and the structurally similar domain of pyruvate kinase.