A global representation of the protein fold space

Abstract

One of the principal goals of the structural genomics initiative is to identify the total repertoire of protein folds and obtain a global view of the "protein structure universe." Here, we present a 3D map of the protein fold space in which structurally related folds are represented by spatially adjacent points. Such a representation reveals a high-level organization of the fold space that is intuitively interpretable. The shape of the fold space and the overall distribution of the folds are defined by three dominant trends: secondary structure class, chain topology, and protein domain size. Random coil-like structures of small proteins and peptides are mapped to a region where the three trends converge, offering an interesting perspective on both the demography of fold space and the evolution of protein structures.

Figure 1

The first 20 eigen values of the metric matrix calculated from the 498 × 498 dali structural alignment scores.

Figure 2

A 3D representation of the protein fold space. Each sphere represents a protein fold family. Protein folds that belong to the α, β, and α/β scop classes are clustered mostly around three separate axes, α (red), β (yellow), and α/β (cyan). Most protein folds of the α+β class (blue) fall between the α and β axes and on or near the plane defined by the α and β axes. The α and β axes approximately intersect at one point indicated by the green ball.

Figure 3

The three factorial axes defined by the eigen values of the metric matrix. (A) The first two axes discriminate among α, β, and α/β folds (color scheme the same as Fig. 2). (B) The third factorial axis correlates with the change in protein domain size, corresponding to a dominant trend in the distribution of folds in the fold space.

Figure 4

Comparing the fold usages between two species in the eubacterial domain (Chlamydia versus Aquifex, A) and between two species representing two different domains (Chlamydia of bacteria versus Halobacterium of archaea, B). Structural annotations of the ORFs encoded by each genome are obtained by a blast search against the scop sequence database. Percentage of the annotated ORFs in a genome that adopts a particular fold defines the usage of the fold by the organism. The usages of the 498 folds by the second organism are subtracted from the fold usages by the first organism. A contour surface (mesh) is then constructed and set at the values of 0.4% for blue and −0.4% for red. Regions within the blue contour include folds that appear more frequently in the first organism, whereas regions within the red contour include folds that occur more frequently in the second organism.