Protein Secondary Structure: Alpha Helices and beta Sheets and Hydrogen Bonds
Descriptions of the basic principles of protein structure, including the secondary structure, may be found in many good quality biochemistry books. Here I will focus on the general aspects, which are important to keep in mind, for example, when analyzing a sequence alignment, when making a homology model and analyzing model quality, when planing some mutations in you protein or when analyzing the interactions of your ligand with a protein.
The most common type of secondary structure in proteins is the alpha-helix. Linus Pauling was the first to predict the existence of the alpha-helix, which was confirmed with the determination of the first three-dimensional structure of myoglobin by Max Perutz and John Kendrew. An example of an alpha-helix is shown on the left 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, I removed the amino acid side chains in this figure. Notice how all the carbonyl oxygen atoms (shown in red) point in one direction, towards the C-terminal end of the helix. To be more exact, they actually point towards the amide nitrogen of the amino acid, which is 4 residues away in the sequence. Together they form a hydrogen bond, one of the main factors in the stabilization of secondary structure in proteins.
On the right the same alpha-helix is shown, but with dashed lines representing the hydrogen bonds. For a hydrogen bond to be formed two electronegative atoms (in the case of an alpha-helix the amide N, and the carbonyl O) have to interact with the same hydrogen. The hydrogen is covalently attached to one of the atoms (called the hydrogen-bond donor), but interacts electrostatically with the other (the hydrogen bond acceptor, O). In proteins almost all groups capable of forming H-bonds (both main chain and side chain atoms), independently of whether the residues is within a secondary structure or some other type of structure, are usually H-bonded to each-other or to water molecules. Due to their electronic structure, water molecules may accept 2 hydrogen bonds, and donate 2, thus being simultaneously engaged in the total of 4 hydrogen bonds. Water may also be involved in the stabilization of secondary structure. It is useful to remember that the energy of a hydrogen bond, depending on the distance between the donor and the acceptor and the angle between them, is in the range of 2-10 kcal/mol.
Hydrogen bonds also stabilize another type of secondary structure in proteins, namely the beta-sheets. An example of a beta-sheet with the stabilizing hydrogen bonds is shown on the figure below:
Hydrogen bonds also stabilize another type of secondary structure in proteins, namely the beta-sheets. An example of a beta-sheet with the stabilizing hydrogen bonds is shown on the figure below:
As you may see from this figure, the hydrogen bonds in this case are between different stretches of the structure. By other words, they are not formed between residues adjacent to each other, as in the case of an alpha-helix. Rather, different stretches of the amino acid sequence of the protein form a beta-sheet. Each stretch of sequence in a beta-sheet is called a beta-strand. Thus, a beta-sheet consists of several beta-strands, kept together by a network of hydrogen bonds.
The same beta-sheet is shown on the figure below, this time in a so-called "ribbon" representation, and in the contexts of the protein structure to which it belongs (protein colored according to secondary structure, yellow-beta-sheets and magenta-helices). The arrows show the direction of the beta-sheet, which is from the N-terminus to the C-terminus. When the arrows point in the same direction, we call such a beta-sheet parallel, and when they point in opposite directions, the beta-sheet is called anti-parallel.
The same beta-sheet is shown on the figure below, this time in a so-called "ribbon" representation, and in the contexts of the protein structure to which it belongs (protein colored according to secondary structure, yellow-beta-sheets and magenta-helices). The arrows show the direction of the beta-sheet, which is from the N-terminus to the C-terminus. When the arrows point in the same direction, we call such a beta-sheet parallel, and when they point in opposite directions, the beta-sheet is called anti-parallel.
In the next figure you can see an example of a protein structure with an anti-parallel beta-sheet. Notice that the arrows point in different directions in this case.
When we just have 2 beta-strands anti-parallel to each other, like in the figure below, we call this secondary structure a beta-hairpin. The part between the two beta-strands is called a loop. Loops are considered to be one of the secondary structure types in proteins. They play an important role, connecting together beta-strands or strands to alpha-helices, or helices to each other. Loop sequence within a particular protein family may be very variable. For this reason, as it is discussed in the sequence alignment and homology modeling parts, when aligning homologous sequences, we try to localize insertions and deletions to loop regions. There are different types of loops, depending on the types of the amino acids there, and on the torsion angles within a loop, but for our purposes we don’t need to go into these details now.
A beta-hairpin
You may always return to the summary page of the protein structures chapter, if you would like to jump to some other parts. In the next section I will discuss an important characteristic of the secondary structure of proteins, the torsion angles and the Ramachandran plot.