Proteins have unique three-dimensional shapes and carry out a wide variety of organism functions. Their shape is determined by interactions between the chemical groups of amino acid residues.
Each amino acid has a side chain with different properties. Polar side chains form hydrogen bonds and nonpolar side chains interact via weak van der Waals interactions.
Primary
The primary structure of proteins is the linear sequence of amino acid residues in a polypeptide chain. This is encoded by the DNA in our cells, and is the information that proteins are built from. Proteins are made from chains of amino acids that are held together by covalent peptide bonds between the N and C termini of each amino acid. These peptide bonds are highly resistant to heat and chemicals. Mutations in a single amino acid residue can change the protein’s shape and function. For example, an amino acid substitution in the sequence of hemoglobin can cause sickle cell anemia.
After synthesis the amino acid chains fold into shapes called secondary structures. This is where the proteins get their distinctive shape, and it is responsible for a large portion of their tensile strength. Proteins can fold in many ways, but two of the most common are alpha helix and beta-pleated sheets. Alpha helix is a coil that has the characteristic shape of a snake, while beta-pleated sheets are flat.
Within these structures parts of the protein can adopt specific repeating patterns, or motifs, that give the protein its distinct shape. For example, the amino acid residues in the backbone can be hydrogen bonded into an a-helix or a b-pleated sheet.
Turns, loops, hairpins and flexible linkers are other motifs that can be found in protein secondary structures. Some proteins have both a-helix and b-pleated sheets, while others contain only one type of secondary structure. The overall three dimensional shape of a protein, called the tertiary structure is the result of further folding and twisting of the secondary structure into a fibrous or globular shape. Hydrogen bonds, electrostatic forces and disulfide bridges stabilise the tertiary structure.
Secondary
The secondary structure of a protein is the regular folding into specific structural patterns of regions within a polypeptide chain. These patterns are stabilized by hydrogen bonds involving the carboxyl oxygen of the peptide bond with the amino hydrogen of the adjacent amino acid. Two of the most common patterns are alpha helices and beta pleated sheets. Other folding patterns such as turns and omega loops may also occur.
The side chains of the individual amino acids may form ionic or covalent bonds with other amino acid side chains to create these patterns. The three-dimensional shape of a protein, called the tertiary structure, is influenced by the secondary structure but is primarily determined by interactions between ionic or covalent bonds and disulfide bonds formed by sulfur-containing side chains.
These local structures spontaneously form as an intermediate between the linear amino acid chain and its final globular shape. The amino acid sequence can be used to predict some of the secondary structure but other structures such as helixes, beta strands, and omega loops are more difficult to determine. The secondary structures of proteins are characterized as 3 general states: G (310 helix), H (a-helix), and E (beta strand in parallel or anti-parallel b-sheet conformation). Other characterizations include sharp turns, omega loops, and coil.
Tertiary
Proteins have a specific three-dimensional shape, called the tertiary structure, which is fashioned by many stabilizing interactions. For example, hydrogen bonds between the carbonyl oxygens of peptide bond amide hydrogens and amino acid side-chain groups play an important role in folding, while ionic interactions (attraction between unlike electric charges of ions) contribute to tertiary structure stability. Disulfide bonds (covalent links between the sulfur-containing side chains of cysteine residues) also stabilize tertiary structures.
As the name suggests, tertiary structures are a step up from the secondary structures of alpha-helices and beta-pleated sheets. The tertiary structure of proteins is typically compact and well-defined. It may contain regions of secondary structure or none at all, but if it contains multiple overlapping sections of secondary and tertiary structures, it is called a quaternary structure.
The quaternary structure of proteins is usually a highly organized collection of globular protein subunits. The quaternary structure is held together by a wide variety of non-covalent interactions and disulfide bonds. It is the most stable of all levels of protein structure, but it can still be disrupted by stress factors such as heat, pH changes, removal of water or metal ions.
The information for a protein’s tertiary structure is encoded in the sequence of its amino acids. For example, the tertiary structure of the enzyme ribonuclease is defined by its amino acid sequence as follows:
Quaternary
The quaternary structure of proteins consists of the specific association of folded protein chains or subunits into an oligomer (oligo = several; mer = body) with a defined spatial arrangement. It is the fourth level of the protein structural hierarchy and is determined by non-covalent interactions between complementary surface hydrophobic regions on different polypeptide chains. These interactions may also involve basic or acidic side chains that form salt linkages. Some proteins contain covalently bound disulfide bonds that stabilize quaternary structure as well.
Proteins with quaternary structures are usually multiprotein complexes. In some cases, such as the ribosome, these complexes are made up of multiple identical proteins. Such multiprotein complexes are sometimes referred to as holoenzymes. In other cases, quaternary structure consists of heteromultimers, in which the functional core is made up of one subunit while the regulatory or structural components are made up of a different set of homologues.
The quaternary structure of proteins can be determined by a number of experimental techniques. For example, the mass of a sample of native protein in a variety of conditions is measured using a technique called MALDI-TOF mass spectrometry or by SDS-PAGE after first treating the complex with chemical cross-linking agents to break down its primary structure. This information, together with knowledge of the stoichiometry and/or mass of the individual subunits, allows the quaternary structure to be predicted with a given accuracy.