4.0 Beta sheet supersecondary structures

These structures are formed from combinations of two or more beta strands.

4.1 Beta hairpins

• Beta hairpins are one of the simplest, and most abundant (in globular proteins), supersecondary structures involving beta sheets

• Figure 4.0 and Figure 4.1 shows that the hairpin consists of two antiparallel beta strands connected by a loop and as its name suggests it looks like a hair pin!

• The loop of the hairpin can contain from 2 to 16 residues (see Loops) although about 70% of beta hairpin loops contain less than seven residues with two residue beta hairpins the most prevalent (Sibanda and Thornton, 1985). Longer loops between strands from a beta-meander (Figure 4.2)

• If the loop is small and contains two residues then a beta turn (or reverse turn) joins the two beta strands. Type I' and Type II' reverse turns are most common secondary structure joining the two strands because they have less steric hindrance with the sheet than either the Type I and Type II turns.

• presently no known function

4.2 Beta corner

• Two antiparallel beta strands which form a beta hairpin can change direction abruptly. The angle of the change of direction is about 90 degrees and so the structure is known as a 'beta corner' as shown in Figure 4.3.

• The abrupt angle change is achieved by one strand having a glycine residue (so there is no steric hindrance from a side chain) and the other strand having a beta bulge (where the hydrogen bond is broken).

• no known function

4.3 Greek key motif

• The Greek key motif is another frequent beta sheet motif found in protein structures and is formed from four adjacent antiparallel beta strands.

• The pattern of these strands resembles the pattern seen on Greek urns (Figure 4.4) - hence the name.

• The essential features of this pattern are that :
  1. four sequentially connected beta strands adjacent to each other (note that 'adjacent' does not always mean geometrically aligned to each other as may be expected from Figure 4.4)
  2. alternate strands run in the opposite direction (as you may expect because this is an antiparallel sheet)
  3. the first strand (N-terminal strand) and last strand (C-terminal strand) are adjacent to each other and hydrogen bonds exist between them
  4. connecting loops can be long and include other secondary structures

   

• no known function

• Figure 4.5 shows an example of a Greek key motif in gamma crystallin (an eye lens protein)

4.4 Determination of Secondary (and supersecondary) Structure

In this course we haven't touched upon the principles, and assumptions, involved in the determination of any secondary and supersecondary structure (but please refer to Dr Kurt Berndt's site).

However, you should note that determination of secondary structure is difficult, can be subjective, and hence can be open to various interpretations. This difficulty is compounded in supersecondary structures, because we are trying to determine the association of various secondary structure elements which comprise it.

The visualisation of secondary structures depends upon:

• the information provided in the crystal (or nmr) structure (contained in the pdb file)

• or if no information is given, by the calculation of secondary structure by the computer program used to visualise the protein.

• This information may, or may not, be consistent with what we might 'expect to see' in the protein.

For example, when you examine the secondary structures in Staphylococcus nuclease (Figure 4.6) with RasMol you may find it difficult to immediately identify the Greek key motif. The difficulty lies in the way the program shows the beta strands (from information provided in the pdb file) and the fact that the adjacent strands are not parallel to each other (Does this problem still exist using Jmol?).

The program shows the first beta strand of the Greek key motif in two pieces - a strand comprising residues 6-10 and a strand comprising residues 13 to 19. Consequently, it is difficult to identify where the first strand and last strand of the motif are 'adjacent' to each other.

However, if the first strand is taken as including residues 6 to 19 (no break) then you can see how this long first strand (N-terminal) is adjacent to the shorter last strand (C-terminal) Figure 4.7.

4.5 Topology Diagrams

A topology diagram like Figure 4.4 aims to help make the identification, and relationship, between each of the secondary structural elements simpler, clearer, and to 'map' the structures in two dimensions (2D).

Unfortunately, this particular diagram can inadvertently mislead the reader, because it suggests that the elements of the Greek key structure all lie in the same plane.

An alternative, and better, topology representation is that used by TOPS (Topology Of Protein Structures) where secondary structures are represented by symbols: triangles represent beta strands and circles represent helices. Essentially, you can think of the TOPS diagram as a 'top view' of the secondary structures within a protein. The basics are explained by TOPS as follows:

• Each secondary structure element has a direction (N to C) which is either "up" ( out of the plane of the diagram ) or "down" (into the plane of the diagram).

• Direction of elements can be deduced from the connecting lines. If the N terminal connection is drawn to the edge of the symbol and the C terminal one to the centre of the symbol then the direction is up; otherwise, the N terminal connection is drawn to the centre and the C terminal one to the edge and the direction is down.

• The direction information is duplicated for strands. "Up" strands are indicated by upward pointing triangles and "Down" strands by downward pointing triangles.

Please see TOPS for a more detailed explanation of this topology system.

Figure 4.8 and Figure 4.9 shows the topology diagrams of Adenovirus type 5 fiber protein and Staphylococcus nuclease respectively. See if you can pick the Greek key motif in both diagrams.