Alpha/Beta Barrels

How are these six proteins similar? They all perform very different functions: they represent five different classes of enzymes, and one is a non-enzymatic protein. They all have very different oligomeric structures, ranging from monomeric to decameric assemblies. They all have very different chain lengths. However, in spite of these differences, they all have one central similarity: they all fold into a classic alpha/beta barrel.

Finding Folds

Researchers at JCMM and JCSG have been analyzing the genome of the bacterium Thermatoga maritima to discover similarities like this. Using information in the genome and known structures of proteins, they reconstructed a model of the central metabolic network of the bacterium, defining the proteins and small molecules that perform the major processes of life. The result is a network of 478 proteins (120 with known structures, and the rest modeled) and 503 small molecules, all interacting in 645 reactions.

Evolving Functions

Given this comprehensive information, we can now start asking interesting questions about the evolution of self-sustaining organisms. It has been known for some time that many proteins have similar folding patterns, and several hypotheses have been proposed to account for this. It could be that a stable protein fold (like the alpha/beta barrel) evolves once, and then diversifies through gene duplication to create many similar enzymes with different functions. Alternatively, proteins with many different folds can evolve separately to perform similar functions.

Network Analysis

The network analysis reveals, as is often the case with biology, the cells take all of these approaches. In this bacterium, about 11% of the proteins are examples of similar structures performing similar functions. However, many examples are also found of enzymes with similar function but very different structures. The six proteins shown here are examples of yet another relationship, where a particularly successful folding pattern (the alpha/beta barrel) is used in many different functions.

TIM Barrels

The alpha-beta barrel is the most common protein fold found in Thermatoga maritima. In these proteins, the chain forms a series of alternating alpha helices and beta sheets, which then wrap into a stable, cylindrical structure. This fold is often called a "TIM barrel" because there is a particularly symmetrical example in the enzyme triose phosphate isomerase (shown here from PDB entry 1tim). You can click on the TIM barrel image to get a Jmol of the six proteins from Thermatoga, all overlapped to show the similarities and differences between their folding patterns (PDB entries 1vkf, 1zy9, 1o0y, 1j5s, 1vrd and 1vpx).

References

1. Zhang, Y. et al. Three-dimensional structural view of the central metabolic network of Thermatoga maritima. Science 325, 1544-1549 (2009).