9.0 Alpha/Beta Tertiary Structure

Alpha/beta tertiary structural domains occur in proteins with one domain (eg. adenylate kinase, carboxypeptidase, thioredoxin, subtilisin, and triosephosphate isomerase), and occurs at least once in proteins with two domains (eg. lactate dehydrogenase, malate dehydrogenase, and alcohol dehydrogenase), or three domains (eg. Tyr-tRNA synthetase and glutathione reductase). Here are the main points...

• Most frequent domain class

• The beta strands making up these domains are all essentially parallel (although do sometimes have mixed beta sheets)

• Alpha helices and beta strands tend to alternate along the polypeptide chain

• Consists of an 'outer layer' of alpha helices and an 'inner core' of beta sheets

• Presence of recognised supersecondary motifs primarily beta-alpha-beta motifs and the beta-alpha-beta-alpha-beta motif (otherwise known as the Rossmann fold)

• loop regions joining the secondary structural elements within this domain often form binding areas or crevices for active sites or ligand binding. If the loop acts as an active site in an enzyme then the enzyme activity and specificity seems to be determined by the length and composition of the loop.

• There are presently (as of version 1.39) about 84 subclasses listed in SCOP for this domain, and some examples of these are outlined below.

9.1 Alpha/beta barrel

Figure 9.1 shows that beta strands essentially form a barrel (with a hydrophobic core in the centre of the barrel) surrounded by alpha helices which run parallel to the axis of the barrel.

This domain structure is also called 'singly wound' because of the one-way direction of the sheets and the way the helices are oriented around the sheets as shown in Figure 9.2

One of the largest domain structures - need about 200 residues to form the domain with a minimum of about 8 beta strands

Quite a few glycolytic and transport proteins have this structure eg.triosephosphate isomerase (Figure 9.1), pyruvate kinase, aldolase, phosphoglucomutase, enolase, ribulose bisphosphate carboxylase, glycolate oxidase.

The active site of this structure is in a pocket (or funnel) formed from the loop regions that connect carboxy ends the beta strands with the adjacent alpha helices - Figure 9.3

Often seen as the active site domain in multi-domain proteins

9.2 n-layer Sandwich

This domain describes the structure where the beta sheet and alpha helices are arranged in 'layers' similar to a multi-layered sandwich.

The number 'n' indicates the layers of either beta sheets or alpha helices and generally ranges from 2 to 4.

The 2 layer sandwich has a beta sheet and alpha helix in two layers (beta|alpha). The 3 layer sandwich can have either (alpha|beta|alpha) or beta|beta|alpha in the three layers. The 4 layer sandwich usually has the alpha|beta|beta|alpha in the layers.

Quite a few glycolytic and transport proteins have this structure including: lactate dehydrogenase, flavodoxin, phosphogycerate mutase and hexokinase

Figure 9.4 shows the three layer sandwich of carboxy lyase.

This domain structure is also called 'doubly wound' because of the two-way direction of the sheets and the way the helices are oriented to one either side of the sheets as shown in Figure 9.5

9.3 Alpha/beta horseshoe

As the name suggest this structure resembles a 'horseshoe'.

This domain has an ordered, and tightly curved, beta sheet surrounded by alpha helices which run antiparallel to the strands.

Figure 9.6 shows this domain in ribonuclease inhibitor.