Protein Secondary Structure: α-Helices and β-Sheets

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 figure below. This type of representation of a protein structure is called sticks representation. To give you a better impression of how a helix looks like, only the main chain of the polypeptide is show in the figure, 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 φ values and ψ values, observed as mentioned earlier in the text, as clustering of the corresponding torsion angles within the helical region of the Ramachandran plot. The α-helix is the major structural element in proteins. When looking at the helix in the figure below, we notice how the carbonyl oxygen atoms C=O (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 right figure as dashed lines.

alpha-helix example
hydrogen bonds stabilize alpha-helices

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. A paper describing the occurrence of the π-helix in proteins, which is based on the analysis of entries in the Protein Data Bank (PDB) has been published by Fodje & Al-Karadaghi, 2002.

The second major type of secondary structure 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. An example of a β-sheet with the stabilizing hydrogen bonds shown as dashed lines is shown on the figure below:

beta-sheet hydrogen bonds

The figure shows how hydrogen bonds link different segments of the polypeptide chain. These segments do not need to follow to each other in the sequence and may be located in different regions of the polypeptide chain.

The same β-sheet is shown on the figure below, 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). In the figure each β−strand is represented by an arrow, which defines its direction starting from the N-terminus to the C-terminus. When the strand arrows point in the same direction, we call such β-sheet parallel:

parallel beta-sheet

When the strand arrows point in opposite directions, the sheet is anti-parallel. In the next figure you can see an example of a protein structure with an anti-parallel β-sheet:

anti-parallel beta-sheet

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 β-turn, when it is short. 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) are usually shorter that their mesophilic counterparts, presumably to give a protein additional stability at high temperatures, preventing its denaturation. Loop length in a protein family may be very variable, which justifies, as it is discussed in the sequence alignment and homology modeling, the localization of insertions and deletions to loop regions.

beta-hairpin structure

You may have heard the expression "Structure is Function". Structural motifs are of course part of the structure and are closely linked to protein function. For this reason, when working or just viewing 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 look at some of the ways by which secondary structure elements may be connected to each other, forming common structural motifs. To create the observed variety of protein structures, proteins use these structural motifs as building blocks.