Primary Structure of Proteins
Two amino acids generate a peptide bond to connect them together by losing a water molecule. The third, fourth, and up to the Nth amino acid are linked in a same way. They are akin to a word. Different numbers and types of letters create different words. No matter the length of peptide chain, its ends are always an amino or carboxyl group. The covalent peptide bonds is extremely robust. The primary structure determines higher-order structures, as the arrangement of amino acids allows us to deduce protein structure.
Two sulfhydryl groups can link together to form a disulfide bond. These bonds exist not only between different regions of the same peptide chain but also between different peptide chains. Certain folds and higher-order structures are maintained by disulfide bonds. It’s a weak covalent bond that can be broken and reformed easily. This dynamic nature is beneficial for regulating protein biological activity.
Secondary Structure of Proteins
Hydrogen bonds create secondary structure in polypeptide chains. They don’t originate from side groups but from the peptide bond (-CO-NH-). The partial positive charge in hydrogen atom and the partial negative charge in oxygen atom forms a hydrogen bond.
α-Helix
α-helix is the most common and abundant secondary structure in proteins. Parts or entire peptide chain has a regular helical conformation along its axis. The R groups in amino acids are located on the exterior of helix. On average, each helix turn contains 3.6 residues. The hydrogen bond between carbonyl oxygen in nth residue and amide proton in (n+3)th residue is the main factor to maintain this structure. Right-handed helices are the most common conformation, although left-handed helices also occur.
Whether a helix will occur in peptide chain is highly related to amino acids R groups. Helices are easily found in small neutral R groups, such as methyl groups. Polyalanine spontaneously coils into an α-helix in pH 7 aqueous solutions. Regions rich in acidic or basic amino acids are less likely to form helices. In neutral solutions, polylysine is randomly exist due to repulsion between positively charged R groups, but it can spontaneously generate an α-helix in alkaline solutions when the positive charges are neutralized.
In addition to charge, R group size also influences helix formation. Some R groups are so large that they obstruct space even on the exterior, such as amino acids with benzene rings. These not only have large volumes but also their hydrophobic character makes them tend to cluster with other lipophilic groups.
β-Sheet
Parallel polypeptide chains construct a regular repeating structure through hydrogen bonds. You think of them as folded paper strips arranged in parallel. The polypeptide chains are zigzag along strips, and the α-carbons are always on crease. R group are placed on upper and lower sides of paper alternately to avoid steric hindrance.
The carbonyl group in one polypeptide chain forms a hydrogen bond with amide proton of an adjacent chain. Almost all peptide bonds participate in β-sheets that are in parallel or antiparallel type. In antiparallel β-sheets, N-termini point in opposite directions. This type is more stable because hydrogen bonds are nearly perpendicular to polypeptide chains. N-termini in parallel β-sheet are in the same direction. Their hydrogen bonds are angled slightly and less stable.
β-Turn, β-Bulge
Most proteins are globular that require bends and turns in the polypeptide chain to satisfy this shape. Non-repetitive structures like β-turns and β-bulges serve this purpose. In β-turns, the carbonyl group in nth peptide bond and the amide proton in (n+4)th peptide bond are connected by hydrogen bond to create a very stable loop that turns the polypeptide chain 180°. Proline and glycine often appear in β-turns.
β-bulge is another common non-repetitive structure. You can imagine it as an amino acid that inserts into polypeptide chain in β sheet to cause a localized bulge. It doesn’t change the polypeptide direction as sharply as a β-turn but introduces slight bends to accommodate complex three-dimensional structures, such as those near active sites.
Random Coil
It refers to regions without regular α-helix or β-sheet structures. These areas appear disordered, but in fact they have stable and well-defined conformations like other secondary structures. Random coils often constitute enzyme active sites or other functional areas in proteins. They are also situated at surface and domain linkages. These dynamic regions adjust slightly to fit ligands better. For example, many transcription factors contain random coils that aid in their movement along DNA and recognition of specific binding sites.
Tertiary Structure of Globular Proteins
Although fibrous proteins are abundant and essential in organisms, they aren’t very diverse. The complexity and diversity are primarily reflected in globular proteins. Several secondary structural units are combined to form a spherical or ellipsoidal tertiary structure. Hydrophobic groups are buried inside, while hydrophilic groups interact with aqueous environment. It’s also known as active site whose loose structure allows for conformational adjustments upon binding. Hydrophobic interactions, hydrogen bonds, salt bridges and disulfide bonds are involved in the tertiary structure.
Quaternary Structure of Proteins
Monomeric proteins like myoglobin don’t have a quaternary structure, while some proteins with multiple polypeptide chains are more complex. These peptides are called subunits. What connects them are hydrophobic interactions, a few hydrogen bonds and salt bridges, so the quaternary structure is less robust. These subunits must be combined to confer biological activity to protein. Separated subunits can’t perform their bio functions, even if original conformations are retained. C-reactive protein is composed of five identical subunits. Meanwhile, the different subunits are available in protein, such as in hemoglobin.