Structural Motifs & Connectivity Between Secondary Structure Elements

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. The connectivity between secondary structure elements and the type of secondary structure elements involved define the level of structural organization called structural motifs. Here we will look at some examples. It is possible to learn how to distinguish different structural motifs by analyzing a protein structure using graphics display software like Chimera or Pymol.
One of the simplest protein 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 proteins.

helix bundle structure

Parallel and anti-parallel β-sheets may also be connected by different structural elements. The simplest and most common connectivity is made by loops, like in hairpins described earlier. If a connecting region cannot be classified as a secondary structure, and it is not a short loop, it is sometimes called coiled region. Often secondary structure elements may have long coiled (unstructured) regions between them. An example is shown on the figure below.

parallel beta-sheet

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:

TIM barrel domain

Other examples of connectivity in anti-parallel sheets are shown below. In the first 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:

anti-parallel beta-sheet

The figure below shows the topology of a protein plastocyanin, which only contains β–structures. Try to identify the Greek-key motif in the structure:

Plastocyanin anti-parallel beta-sheet

There are of course other types of connectivity between secondary structure elements. Our aim here is to demonstrate the concept by showing some example. In the following sections we will discuss a more general level of organization, folds and domains.