Structural Motifs & Connectivity Between Secondary Structure Elements

In protein structures helices and strands are connected to each other and combined in many different ways. From known protein three-dimensional structures we have learned that there is a limited number of ways by which secondary structure elements are combined. Here we will examine 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 helix bundle (images below shows a 4 helix and 3 helix bundles). Helix bundles are very common in protein structures and are very often found as separate domains within larger, multi-domain proteins.

Clicking the images will take you to the PDB 3D-view:

Parallel and anti-parallel β-sheets may be connected by different structural elements like loops, coil (unstructured) regions, or helixes. 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 called coiled region. Often secondary structure elements have long coiled 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

Examples of connectivity in anti-parallel sheets are shown below. In the first two hairpins are connected to each other, 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

These are just some illustrative examples, there is a large number of other types of structural motifs and connectivity between secondary structure elements not discussed here.
In the following sections we will discuss a more general level of organization, folds and domains.