Core ConceptsThis article provides insight to the different secondary structures of proteins, including alpha-helices, beta sheets, and beta turns and loops.The Building Blocks of LifeProteins have a wide range of roles in various biological systems. Their three-dimensional structures, organized into primary, secondary, tertiary, and quaternary structures, determine their functions. The secondary structure is known by the local, repetitive patters of folding observed in the polypeptide backbone that is stabilized through hydrogen bonds. To understand and explain protein function, stability, and interactions, analysis of protein secondary structure is essential.Levels of Protein StructurePrimary StructureThe primary structure of proteins is defined as the linear sequence of amino acids that make up the peptide chain of a protein. The primary structure is also known as the sequence.Secondary StructureThe secondary structure is the repeating patters within the polypeptide chains, stabilized by hydrogen bonds located between the amides of the backbone. Secondary structure includes several different common forms, including random coil, alpha helix, beta sheet, and more uncommon forms like the 3,10-helix, the pi-helix, and omega loops.Tertiary StructureThe tertiary structure of a protein is the overall three-dimensional folding that occurs to a single polypeptide chain. The tertiary structure can be thought of as how the elements of the secondary structure are oriented in three dimensional space. For example, are two alpha helices parallel to each other? Or are they far apart in space? These structures are stabilized through intermolecular interactions and disulfide bridges.Quaternary StructureThe quaternary structure of a protein describes how many subunits or different amino acid chains make up the overall structure. In many cases, functional proteins are oligomers, such as dimers or trimers. Sometimes, the protein’s quaternary structure involves several different amino acid chains that combine to form a heterodimer or heterotrimer.Common Secondary StructuresAlpha-HelixAlpha-HelixAn alpha-helix is a right-handed coiled structure with the backbone of the polypeptide chain tucked on the inside of the helix and the side chains pointing outwards, avoiding steric clashes. It is held together through hydrogen bonding, which each carbonyl oxygen from the peptide bond forming a hydrogen bond with the amide hydrogen four residues away. This leads to a stabilized helix with 3.6 amino acids per helix turn and a helical distance of 5.4 Angstroms.Why Alpha-Helices FormAlpha-helices form due to the favorable hydrogen bonding patter, which results in a stable and energetically favorable structure. The likelihood of an alpha-helix forming is influences by the amino acid sequence, with residues such as alanine, glutamate, and leucine being highly likely to be found in helices. This is because of the properties that their side chains possess.Beta-SheetBeta-sheets are formed when beta-strands are connected through backbone hydrogen bonds. They can be either parallel, meaning the adjacent beta-strands are in the same direction, or antiparallel, meaning the beta-strands go in opposite directions. Parallel beta-sheets are less stable than antiparallel sheets due to the hydrogen bonding patterns formed between the carbonyl oxygen of one strand and the hydrogen of the amide on an adjacent strand. In all beta-strands, the side chains of the amino acids alternate being above or below the plane of the sheet.Why Beta-Sheets FormBeta-sheets are also a result of specific hydrogen bonding patterns that form between beta-strands. The amino acid sequence also plays a role, with residues such as valine, isoleucine, and phenylalanine being more likely to be found in beta-sheets due to their bulky side chains.Beta Turns and LoopsBeta turns and loops connect alpha-helices and beta-sheets. Beta turns are four-residue segments that switch the direction of the polypeptide chain. Loops, however, are longer regions that connect secondary structural elements and are highly dynamic. Both are essential for the overall folding and function of a protein.Random CoilsRandom coils are part of the protein that don’t form a regular secondary structure. Random coils are flexible and lacking order, resulting in more fluid and dynamic interactions. Glycine and proline are amino acids that are highly likely to be found in random coils due to their conformational flexibility and structural constraints.The Ramachandran PlotThe Ramachandran plot is a valuable tool for describing why certain amino acids have different preferences of conformational properties. It plots the phi (φ) and psi (ψ) dihedral angles of the amino acids, with allowed regions for these angles being shown. Alpha-helices, beta-sheets, and other secondary structures all have specific areas on the plot that they occupy. For example, alpha-helices are found in a specific region of the plot where the angles are more conducive to the formation of a helical structure.Determining Secondary StructuresThere are many different ways to determine a protein’s secondary structure.NMR spectroscopy is useful for analyzing proteins in solution, and can be used to provide information about both the secondary and tertiary structures.X-ray crystallography provides 3D structures of proteins, giving a high-resolution analysis of the secondary structure.Circular dichroism spectroscopy works by measuring the absorption of left and right-handed polarized light, allowing for information to be obtained on the content of alpha-helices and beta-sheets.Cryo-electron microscopy allows for protein structures to visualized at atomic resolutions and is very beneficial for analyzing large complexes.Importance of Secondary StructuresFunction– Specific functions, such a protein activity, can be created through binding sites and catalytic sites created through certain arrangements of secondary structures.Stability– Internal stability can be provided to the protein through secondary structures, This allows for the shape to be maintained, even under physiological conditions.ConclusionUnderstanding protein function and stability is dependent on protein secondary structure. From alpha-helices and beta-sheets to beta turns and loops, there are many secondary structures that can be analyzed using advanced techniques to reveal a greater insight into the building blocks of life. The Ramachandran plot is a helpful tool in this analysis, giving a better understanding into why these structures form.
