Proteins perform many of the functions that keep living systems healthy. They may be structural, regulatory, contractile, or protective.
Like other biological molecules, proteins are stabilized by a complex array of chemical bonds. Upon being formed, they test a number of conformations before they adopt their final shape. These shapes are known as primary, secondary and tertiary structures.
Functions
Proteins are large biological molecules that perform a vast array of functions within organisms. They differ from one another primarily in their amino acid sequence, which dictates their 3-D shape and determines their function. Proteins also perform many other functions, such as catalyzing metabolic reactions, replicating DNA, responding to stimuli and providing structure to cells and tissues. The terms protein and polypeptide are often used interchangeably, but protein refers to the complete protein molecule in a stable conformation, while polypeptide generally refers to a short chain of amino acids without a defined 3D structure.
The amino acids that comprise proteins can be joined together in different ways to make thousands of different types of proteins with a wide variety of structures and functions. Some proteins act as enzymes, which provide sites for other substances to chemically react, while others are signaling proteins that transmit information from cell to cell or tissue to tissue. Still others, such as hormones, maintain proper fluid and acid-base balance and transport nutrients throughout the body.
Structural proteins form the skeleton of cells and compose much of the material in connective tissues like skin, muscle and bone. Other proteins provide support and shape to tissues and organs, while enzymes facilitate the thousands of chemical reactions that occur in living cells. Still others, such as hormones and messenger proteins, coordinate the processes of different cells and tissues.
Secondary Structure
The secondary structure of a protein is the local folding of a polypeptide chain into conformations that are held together by hydrogen bonds between the amino hydrogen and carboxyl oxygen atoms of the backbone. These local structures form as an intermediate state before the protein folds into its three dimensional tertiary structure. The two most common secondary structures are alpha helices and beta pleated sheets. Different amino acids have varying preferences for the formation of these structures. They can be grouped as helix formers (alanine, cysteine, valine, leucine, methionine, and phenylalanine), beta formers (leucine, isoleucine, and tyrosine) and turners (glycine, aspartic acid, asparagine, and proline).
The helix formation is formed when the backbone flexes in one of two arrangements: either parallel or antiparallel, depending on the amino acid side chains. The beta sheet structure consists of short -strands that lie side by side. -strands are usually surrounded by hydrogen bonds from other parts of the protein, forming a globular shape.
Other forces, including ionic bonds, disulfide linkages and van der Waals interactions between polar residues, help stabilize the final three dimensional shape of proteins. Various methods have been used to predict the secondary structures of proteins from their amino acid sequence. Most commonly, these methods rely on the pattern of “favourable” regions in a Ramachandran plot. However, there is still a need for more accurate prediction methods. Specifically, the ability to confidently predict b-strands seems to be a significant area of improvement.
Tertiary Structure
The tertiary structure of a protein is its overall three-dimensional arrangement in space. It is determined by interactions between the amino acid side chains of different regions of the polypeptide chain. These interactions stabilize the secondary structures, such as helixes and b-pleated sheets, into a coherent whole.
The overall shape of proteins determines their specificity and enables them to bind other molecules, such as substrates or cofactors. Examples of proteins with complex tertiary structures include enzymes, antibodies, and hemoglobin. The active sites of these proteins are located in pockets formed by the protein’s tertiary structure.
The most common tertiary structures are alpha-helixes and b-pleated sheet domains. Alpha-helixes consist of a series of nonpolar amino acid residues arranged in a spiral, as shown in the kinemage linked above, and are stabilized by hydrogen bonds between the O and N atoms of adjacent turns. The tertiary structure of b-pleated sheets is similar, but it consists of parallel antiparallel strands packed together with hydrogen bonds between the backbone and carboxyl groups.
Protein tertiary structure is stabilized by interactions between the R-groups of amino acids, as well as by outside polar hydrophilic hydrogen and ionic bonding interactions with solvent water molecules. The hydrophobic core of globular proteins also helps to stabilize the tertiary structure by restricting the surface area of the protein that is exposed to water.
Post-Translational Modifications
Proteins may undergo a number of post-translational modifications, or PTMs, after their synthesis. These are covalent and generally enzymatic alterations of amino acid side chains, affecting the protein’s structure, function or interactions.
These reversible chemical changes, found throughout the cell, are crucial to many of the cellular functions proteins perform. Examples include phosphorylation, the addition of high energy phosphate groups to hydrophobic side chains of serine, threonine or tyrosine. This alters the electrophilicity of a pocket, and can switch enzymes ‘on’ or ‘off’ by changing how easily they interact with their substrates.
Glycosylation is another common PTM, adding carbohydrate groups to proteins. This is most commonly found in the endoplasmic reticulum and Golgi apparatus, and helps proteins attach to membranes and other cells. Lipidation is another PTM, with the attachment of lipids to proteins, which can also change their function. Other PTMs, such as methylation, arginylation and ubiquitination, also alter proteins’ functions.
These reversible chemical alterations can occur at any point during the protein’s lifecycle, from shortly after ribosome translation to after folding and localization is complete. Early PTMs can affect the protein’s aggregation state and direct it to distinct cellular compartments, while later ones can regulate enzyme activity or turn it off. Some reversible PTMs can happen repeatedly during the lifetime of a protein, such as phosphorylation, turning an enzyme on and off as needed.