Proteins come in many shapes and sizes. They can be globular or fibrous, hydrophilic or hydrophobic.
All proteins are made up of a sequence of 20 amino acids. Microorganisms can biosynthesize most of these, while animals must obtain some (called essential amino acids) from their diet.
Once proteins are fully folded, they carry out a variety of functions. These include transporting molecules across cell membranes, transforming chemical signals into intracellular responses, and anchoring structures within the cell.
Amino Acids
Amino acids are organic compounds that combine to form proteins. The 20 common amino acids found in proteins are derived from the carboxyl acid group and an amino group (-NH2). The carboxylic acid group is linked to the amino group by a covalent bond, known as a peptide bond.
Each amino acid has different properties that can influence protein function. For example, some amino acids have polar or charged side chains, while others are non-polar. The polarity of an amino acid relates to its ability to form hydrogen bonds with other amino acids in a polypeptide chain. The amino acids that have polar or charged side chains are found on the surface of a soluble protein, while those with non-polar or neutral side chains are located within the protein interior.
Amino acids also have special features that affect their ionization and solubility. For instance, seven amino acids have ionizable functional groups in their side chains, which allow them to be ionized in solution. These are aspartic acid, glutamic acid, arginine, histidine, lysine, tyrosine and cysteine. The ionizable side chains of these amino acids are responsible for the acidity or basicity of proteins, their solubility in water and lipids and, in some cases, their temperature preference.
Secondary Structure
Secondary structure is the specific geometric shape a protein assumes as a result of intramolecular and intermolecular hydrogen bonding of its amino acid amide groups. This structure is directly related to molecular geometry concepts and the principle of hybridization theory. Alpha () helices and beta () pleated sheets are two of the most common secondary structures. Alpha helixes are tightly coiled in the form of a spring, with the peptide backbone and side chains extending outward from it. Beta sheets are flat, kinked sheets of parallel or antiparallel chains of amino acids. They make up the core of many globular proteins.
Secondary structures spontaneously form as an intermediate before proteins fold into their three-dimensional tertiary structures. The folding is assisted by a combination of van der Waals interactions, hydrogen bonds, electrostatic forces and disulphide bridges.
Alpha helixes and beta sheets have specific sequence-dependent conformational preferences. The amino acids proline and glycine, for example, prefer helix conformations; tyrosine and phenylalanine favor beta strands. The resulting protein structures are known as structural motifs and may have a functional role in their protein domains. X-ray crystallography, NMR spectroscopy and circular dichroism spectroscopy are used to determine protein secondary structures. The next level up from the protein’s secondary structure is its tertiary structure, the particular three-dimensional arrangement of all its structural elements.
Tertiary Structure
The tertiary structure of proteins gives them their characteristic 3-dimensional shape, allowing them to adopt a specific globular structure. This 3-dimensional shape determines how the protein interacts with other proteins and other molecules.
The structure of a protein is stabilized at the tertiary level by a network of hydrogen bonds, ionic interactions and disulfide bridges formed between amino acid side chains. Hydrogen bonds form between amino acids that are close together in the sequence (hydrophilic contacts) and between the polar and non-polar residues. These hydrogen bonds are important for the formation of alpha helices and beta sheets. They also give the proteins their overall stability, preventing them from unfolding in the cellular environment.
In addition, ionic interactions (attraction between like electric charges of ionized amino acid residues) and disulfide bridges between amino acids with the same charge or opposite charge help stabilise protein secondary structures such as helixes and b-strands. The tertiary structure is also stabilised by hydrogen bonding between the carbonyl groups of the backbone and amine functional groups found on the amino acid side chains.
Some proteins have very complex tertiary structures such as TIM barrels (named after triosephosphate isomerase, a conserved metabolic enzyme). Other proteins contain structural motifs that are similar to each other but have no common evolutionary ancestor, and can arise by convergent evolution.
Quaternary Structure
Proteins are made up of multiple polypeptide chains, known as sub-units. The arrangement of these sub-units in a protein complex is known as the quaternary structure of the protein. This is a stable three dimensional conformation of the protein and depends on interaction between different protein chains or sub-units. These interactions can be covalent or non-covalent. Examples of proteins that have a quaternary structure include hemoglobin, DNA polymerase and ribosomes.
The tertiary structure is the overall shape of a protein and results from further folding of the secondary structures into alpha-helix and beta sheets. This gives the protein its characteristic globular shape. It is stabilised by hydrogen bonds, ionic bonds and disulphide bridges between different amino acid residues.
This is the highest level of protein structure and is responsible for protein function. It is the conformation of a protein that determines its unique shape that allows it to do whatever job it was coded for. If just one amino acid were omitted or swapped, the protein would not have the correct shape and could not do its job.
The quaternary structure also contains loops which are unstructured regions of the protein, found between other regular secondary structure elements. These are held together by a variety of other forces including Van der Waals forces between nonpolar side-chains and electrostatic forces.