Structural Motifs & Connectivity Between Secondary Structure Elements

In the previous section we discussed protein secondary structure. The next level of structural organization is a structural motif, which is defined by the type of connectivity between secondary structure elements, the type of secondary structure elements involved and the by the way they are organized in space. We all know that in protein structures helices and strands are connected to each other and combined in many different ways. Also, from known protein three-dimensional structures we have learned that in nature there is a limited number of ways by which secondary structure elements are combined. Here we will look at just a few examples. In the future you should be able to distinguish such motifs by yourself, for example by using a graphics display program, like SwissPDB viewer (Deep View), Chimera or Pymol.

One of the simplest structural motifs is a helical bundle, shown on the schematic image below. Helix bundles are very common in protein structures and are very often found as separate domains within larger, multi-domain protein molecules.

helix bundle structure

β-sheets may also be parallel and anti-parallel and there are many different connectivity types in this case. Probably the simplest and most common type, which was described earlier, is made by short loops, a hairpin-type of connectivity. When a connecting region in a protein structure cannot be classified as a secondary structure, and it is not a normal loop (which is often relatively short), it is called a coiled region. In the example below the connectivity between strands is created both by helices and coil regions.

Fraction of buried amino acids

In the fold known as the TIM barrel fold (the name is based on the first protein where it was found, Triose phosphate IsoMerase), one of the most widespread type of protein folds, the strands of the β-sheet are parallel, and the connectivity between them is made by α-helices:

Fraction of buried amino acids

Strands within β-sheets may of course be combined in many different ways. Two examples of anti-parallel sheets are shown below. In the first one two hairpins are connected to each other making up the sheet, while in the second there is the so-called Greek-key motif type of connectivity:

Ramachandran plot for well refined structure

The figure below shows the topology of plastocyanin, which is a β–sheet protein. Try to find the Greek-key motif in this structure:

My Image

There are of course other types of connectivity between secondary structure elements. They are described in many books dedicated to protein architecture.
In the next section I will discuss a more general level of organization, protein
folds and domains.