In the following we will focus on the general aspects of protein secondary structure. Many of the features discussed here are essential for practical applications − for example in sequence alignment and analysis, homology modelling and analysis of model quality, in planning mutations or when analyzing protein-ligand interactions.
The most common type of secondary structure in proteins is the α-helix. Linus Pauling was the first to predict the existence of α-helices. The prediction was confirmed when the first three-dimensional structure of a protein, myoglobin (by Max Perutz and John Kendrew) was determined by X-ray crystallography. An example of an α-helix is shown on the image below. This type of representation of a protein structure is called “sticks representation”. To get a better impression of how a helix looks like, only the main chain of the polypeptide is shown, no side chains. There are 3.6 residues/turn in an α-helix, which means that there is one residue every 100 degrees of rotation (360/3.6). Each residue is translated 1.5 Å along the helix axis, which gives a vertical distance of 5.4 Å between structurally equivalent atoms in a turn (pitch of a turn). The repeating structural pattern in helices is a result of repeating (similar) φ and ψ values, which is reflected in the clustering of the torsion angles within the helical region of the Ramachandran plot. When looking at the helix in the figure below, notice how the carbonyl (C=O) oxygen atoms (shown in red) point in one direction, towards the amide NH groups 4 residues away (i, i+4). Together these groups form a hydrogen bond, one of the main forces in the stabilization of secondary structure in proteins. The hydrogen bonds are shown on the figure as dashed lines.
The α-helix is not the only helical structure in proteins. Other helical structures include the 3_10 helix, which is stabilized by hydrogen bonds of the type (i, i+3) and the π-helix, which is stabilized by hydrogen bonds of the type (i, i+5). The 3_10 helix has a smaller radius, compared to the α-helix, while the π-helix has a larger radius. The first detailed analysis of the occurrence of the π-helix in proteins, based on the analysis of entries in the Protein Data Bank (PDB), was published by Fodje & Al-Karadaghi, 2002.
We should also note that in addition to the “simple” helical structures mentioned here, there is a number of so-called coiled-coil structures, in which two or more α-helices together build higher-order helical structures.
The second major secondary structure element in proteins is the β-sheet. β-sheets consist of several β-strands, stretched segments of the polypeptide chain kept together by a network of hydrogen bonds between adjacent strands. An example of a β-sheet, with the stabilizing hydrogen bonds between adjacent strands (shown as dotted lines), is shown in the image below:
It is important to note that unlike in helices, the residues informing hydrogen bonds between the adjacent strands are separated from each other by long segments of the amino acid sequence.
In the following image the same β-sheet is shown, this time in the context of the 3D structure to which it belongs and in a so-called "ribbon" representation (the coloring here is according to secondary structure - β-sheets in yellow and helices in magenta). Each β−strand is represented by an arrow, which defines its direction starting from the N- to the C-terminus. When the strand arrows point in the same direction, we call such β-sheet parallel (the protein PDB code is 1G8P, BchI subunit of magnesium chelatase). You may also notice a β-hairpin, two strands connected by a loop in the left corner of the image:
In the image below you can see that the strand arrows point in opposite directions, which is a characteristic of an anti-parallel β-sheet (this protein PDB code is 1USR, Newcastle disease virus hemagglutinin-neuraminidase).
Loops, turns and hairpins
When there are only 2 anti-parallel β-strands, like in the figure below, it is called a β-hairpin.
The loop between the two strands is called a β-turn. Short turns and longer loops play an important role in protein 3D structures, connecting together strands to strands, strands to α-helices, or helices to helices. The amino acid sequences in loop regions are often highly variable within a protein family. But in some cases, when a loop has some specific function, for example interaction with another protein, the sequence may be conserved. Loop length in proteins from organisms living at elevated temperatures (thermophilic organisms) is usually shorter than in protein from lower-temperature family members, presumably to give a protein additional stability at high temperatures, preventing its unfolding and denaturation. During sequence alignment and homology modeling, when it is essential to have an accurate sequence alignment, the highly variable length of loop regions justifies the localization of insertions and deletions in the amino acid sequence to loop regions.
Structural motifs that contain combinations of helices, helices and strands, etc., are closely linked to protein fold. For this reason, when viewing a protein 3D structures, it is an advantage to be able to recognize the secondary structure elements and to identify structural motifs. In the next section we will examine some of the ways by which secondary structure elements connect to each other, forming common structural motifs and folds.