단백질보충제 Proteins perform a vast array of functions within organisms: catalyzing chemical reactions, binding molecules, transporting substances and providing structural support. They are the workhorses of cells.
Proteins consist of long chains of amino acid residues, which fold into unique three-dimensional shapes. The structures are held together by a variety of chemical bonds, including hydrogen bonds, ionic bonds and disulfide bridges.
Amino Acids
Amino acids are the building blocks of proteins. They join together by condensation reactions to form short polymer chains called peptides or longer ones called proteins. The sequence and number of amino acids in a protein determines its shape, size, and function. There are 20 standard amino acids that are commonly found in proteins. Each has a characteristic shape, is identified by its uppercase letter or three-letter abbreviation, and is coded for in the genetic material of the cell.
Amino acid side chains carry electrical charges that determine how a protein functions. They can bind metals and form electrostatic interactions that stabilize protein structures within a single protein or between interfacing proteins. Amino acids with charged side chains can also form hydrogen bonds with water molecules.
Each amino acid has one ionizable amine group and one ionizable carboxyl group. These groups can interact with other amino acids to form a covalent bond called the peptide bond. During this reaction, the amine and carboxyl groups lose water, forming a salt molecule, and creating an ion.
Some amino acids, such as cysteine, histidine and lysine, can form 단백질보충제 covalent disulfide bonds with other cysteine residues in the protein. This gives the protein a rigid structure, affecting its secondary structure. Other amino acids, such as proline and serine, can be hydroxylated in the presence of Vitamin C (ascorbate), which increases its flexibility. The hydroxyl group of serine can also be phosphorylated by some protein kinases.
Secondary Structure
Protein secondary structure refers to the local folds that form around a polypeptide chain’s backbone. Two of the most common secondary structures are the alpha helix and beta pleated sheet (shown in the image above). Other secondary structures can also be formed, such as turns and loops.
Secondary structure forms when atoms on the backbone of a polypeptide chain interact with each other, forming hydrogen bonds between the carbonyl oxygen of one amino acid and the amide hydrogen of another amino acid. This interaction gives rise to local patterns of a particular shape that help give the protein its overall shape. The two most common secondary structures are helixes and sheets, both of which were predicted by Linus Pauling and his colleagues in the early 1950s.
Alpha helices and beta sheets have specific patterns to their hydrogen bonding; these are determined by the nature of the amino acids that form them. For example, proline and glycine prefer to adopt helix conformations, while valine and isoleucine have the ability to form beta sheets.
Some sections of a protein that don’t fit into either helix or sheet have no specific pattern to their hydrogen bonds; these are called loops. Some loops have a role in the function of a protein, while others do not. Loops may have polar or charged side chains, and can interact with other proteins to influence their function.
Tertiary Structure
The tertiary structure of proteins determines their overall shape, which in turn influences their ability to interact with ligands and cofactors. The tertiary structure is stabilized by hydrogen bonding, ionic interactions, dipole-dipole interactions and London dispersion forces between amino acid residues. Proteins with complex tertiary structures include enzymes, antibodies, and hemoglobin. Their tertiary structures allow them to bind to and activate their respective ligands, such as substrates, cofactors or other proteins.
The final step in the protein folding process is the tertiary structure, which results in two major molecular shapes: the alpha helix and the beta pleated sheet. The tertiary structure of the protein is determined by the arrangement of amino acid side chains in regions that are exposed to water, with nonpolar and hydrophobic amino acids clustering together inside the protein, and polar residues leaving water-exposed surfaces for interaction with other molecules.
The tertiary structure of the molecule is also determined by interactions between different parts of the protein chain, which are known as secondary elements. For example, the ribonuclease molecule has an extended secondary element region that forms a loop and is critical for binding to the DNA substrate. In addition, there are many pockets and sites in the tertiary structure of a protein that can bind specific ligands or cofactors. Examples of this include the Y-shaped active site in an enzyme and the heme group in hemoglobin that binds to oxygen.
Post-Translational Modifications
Proteins are highly functionally diverse due to post-translational modifications (PTMs). These reversible chemical additions of functional groups, proteolytic cleavage or covalent attachments of tags to proteins greatly affect many aspects of protein function. Examples of PTMs are phosphorylation, glycosylation, ubiquitination, nitrosylation, acetylation and lipidation. They control protein stability, enzyme activity, protein-protein interactions, protein lifespan, cell-cell and cell-matrix interaction and molecular trafficking. PTMs are also important for signaling, gene expression regulation, DNA repair and cancer.
The number of different types of PTMs is large and is one of the major reasons for the complexity of the proteome. Some PTMs are introduced early in the protein life cycle, before protein folding and localization, to mediate protein folding or stability and to direct the nascent protein to distinct cellular compartments. Other PTMs occur after protein folding and localization to activate or inactivate catalytic functions or to influence protein-protein interactions.
PTMs significantly enhance the coding capacity of proteins to expand proteome diversity, and they play an essential role in many vital cellular processes. Disruption of these cellular processes due to mutations or abnormalities in PTMs has been implicated in disease pathogenesis. High-throughput experimental methods for discovery of PTMs are laborious, and therefore high-level computational prediction methods are needed to facilitate the understanding of the diverse role of proteins in cellular biology and pathogenesis.