previous section previous page next page next section

Online Lectures on Bioinformatics


Analysis of individual sequences

Helical wheels, amphipatic helices and coiled-coils

For many years experimental work on protein structure was concerned almost exclusively with globular proteins. Consequently much of our knowledge now is biased towards this class of proteins and our knowledge on structural proteins or transmembrane proteins is only slowly increasing. Many structural proteins contain amphipatic helices, which consist of hydrophobic, non-polar residues on one side of the helical cylinder and hydrophilic and polar residues on the other side, resulting in a hydrophobic moment. In this way, they aggregate with other hydrophobe surfaces and serve for example as pores or channels in the cell membrame. A helical wheel (see Figure 2) provides a possibility to visualize an amphipatic helix.

Figure 2: Helical wheel representation of an amino acid sequence. The amino acid side chains are projected down the axis (the axis of an alpha helix, orthogonal to the paper plane). As an ideal alpha helix consists of 3.6 residues per complete turn, the angle between two residues is chosen to be 100 degrees and thus there exists a periodicity after five turns and 18 residues. The figure is a snaphot of a Java Applet written by Edward K. O'Neil and Charles M. Grisham (University of Virginia in Charlottesville, Virginia). The applet is accessible at http://cti.itc.Virginia.EDU/~cmg/Demo/wheel/wheelApp.html.

Some amphipatic helices are arranged as intertwined helices that are termed a coiled-coils or super-helices. Generally, a the sequence of an alpha helix that participates in a coiled-coil region will display a periodicity with a repeated unit of length 7 amino acids, which is called a heptad repeat. Denote those 7 positions by a through g, then position a and d are hydrophobic and define an apolar stripe, while there exist electrostatic interactions between residues at positions e and g. Prediction methods for coiled-coil regions ([3][4]) are making use of these preferences. The so-called Leucine Zipper dimerization domains often occur together with DNA-binding domains in regulatory proteins, e.g. eukariotic transcription factors. They form a parallel coiled coil of alpha-helices from two polypeptides chains holding them together. There are only few heptads, usually three to six, whereat the first residue in a heptad is Leucine. A Webservice for Leucine Zipper prediction (see [5]) is available at our site: 2ZIP - Server

exercise 2
exercise 2

Comments are very welcome.