The Structures of Proteins

Proteins are large biological molecules that carry out a wide variety of organism functions, from DNA replication to catalyzing metabolic reactions. They are comprised of linear chains of amino acid residues and stabilized by hydrogen bonds. The unique three-dimensional shape of a protein is determined by the folding patterns of the chains into regions 단백질보충제 called alpha helix and beta-pleated sheets.

Secondary Structure

Secondary structure refers to the local folding of parts of a protein chain. This is usually induced by interactions between the peptide backbone atoms and the amine and carboxyl groups of amino acids. It gives rise to shapes called a-helices and b-pleated sheets. The former is a spiral of hydrogen bonding whereas the latter is a sheet of hydrogen bonds formed between chains that are parallel or anti-parallel to each other.

Other local folds are called gamma turns and beta hairpins. The latter involves a change of direction in the protein chain and has a tendency to involve glycine and proline residues. It is difficult to predict the secondary structure of proteins from the amino acid sequence and hence the structural biology of proteins focuses on how the different elements of the protein come together to form the final structure.

The tertiary structure is the overall three-dimensional shape of the protein and it usually has a globular or ring-like structure. The tertiary structure is stabilized by a wide variety of forces, including hydrogen bonds, disulfide bridges and van der Waals forces. It is also governed by the spatial arrangement of the secondary structures which forms patterns such as helices, b-sheets and extended strands. The quaternary structure is the overall structure of several proteins and is determined by how the various tertiary structures are arranged.

Tertiary Structure

The tertiary structure of proteins is the overall three-dimensional arrangement of all the protein secondary structures in space. It is stabilized by a variety of interactions, including outside polar hydrophilic hydrogen and ionic bonds and internal hydrophobic interactions between nonpolar amino acid side chains (see Figure 4-7). Disulfide bridges, formed by the oxidation of sulfhydryl groups on cysteine residues, and salt bridges, which form between positively and negatively charged sites on amino acid side chains, can also help stabilize tertiary structures.

The three-dimensional shape of proteins determines many of their specific biological functions. A protein’s tertiary structure may be predominantly a helix, a beta pleated sheet or a random coil, but is usually a mixture of these structures. Proteins may also have a globular or fibrous conformation.

A protein’s tertiary structures may be highly stable, but are subject to stress from external factors such as temperature, pH, removal of water, and the presence or absence of metal ions. If these stress factors are great enough, the protein can lose its tertiary or quaternary structures and return to its unstructured form as an amino acid sequence. This process is called denaturation. When a protein denaturates, it loses its ability to function. This is why the protein must be renatured to restore its function. Re-folding a protein is a slow and tedious process, but it can be accomplished by the use of special agents called chaperones, which act as molecular chaperones for proteins.

Primary Structure

The primary structure of a protein is the unique sequence of amino acid residues that makes up its polypeptide chain. It is this sequence that dictates the protein’s three-dimensional shape.

Hydrogen bonding between adjacent amino groups and carboxyl groups of neighboring residues causes proteins to fold and stack into patterns such as alpha helices or beta-pleated sheets. These stable formations are the proteins’ secondary structures.

Alpha helix structures often resemble a spiral. In the kinemage above, you can click on each atom to see its position in this spiral. You can also drag the protein right or left to better appreciate its helix twist. Beta-pleated sheets, on the other hand, are typically parallel to each other. You can drag the kinemage above to better observe this parallel sheet formation, or you can click on individual atoms to see their position in the sheet as a whole.

Like the letters of a word, the amino acids in a protein are arranged with specific “chirality.” This is largely due to the fact that most amino acids have different mirror-image forms. Changing just one of the amino acids in a protein sequence can dramatically alter its structure and function, as is illustrated by diseases such as sickle cell anemia or cystic fibrosis.

Besides beta-pleated sheets and helixes, some proteins can form other types of secondary structures. For example, a covalent disulfide bridge may form between two cysteine amino acids that contain sulphur within their R groups. Hemoglobin, which is shown in the kinemage above, illustrates all four levels of protein structure; it even has quaternary structure, which is formed when multiple polypeptide chains are connected to each other.

Quaternary Structure

The quaternary structure of proteins is the level at which multiple folded protein molecules come together to form functional protein complexes. It is a consequence of the interactions between different segments of a protein’s polypeptide chain. Quaternary structure is the next structural level up from secondary, which refers to local folds that form within a polypeptide chain due to hydrogen bonding between carbonyl oxygen and amide hydrogen atoms of amino acid side chains. These local structures are commonly found in the shape of alpha helices or beta pleated sheets.

These structures are stabilized by interactions between atoms in the polypeptide backbone, such as van der Waals and dipole-dipole interactions, and polar interactions between amino acids. The tertiary structure is also stabilized by covalent bonds, such as disulfide bonds that occur between cysteine residues.

Most enzymes consist of nonidentical subunits, and the specific, noncovalent association of these subunits is called a quaternary structure. The 20S proteasome, for example, consists of two types of ring-shaped protein subunits that arrange in an a/b/a-heptameric structure. The quaternary structure of this protein complex is essential for its function and allosteric regulation. The quaternary structure of other proteins, such as receptor heteromers and cGMP-dependent protein kinases, is also important for their function. Proteins with different quaternary structures can also interact to form larger assemblies, such as protein complexes or oligomers.