Conservation of intrinsic disorder in protein domains and families: II. functions of conserved disorder

Abstract

Regions of conserved disorder prediction (CDP) were found in protein domains from all available InterPro member databases, although with varying frequency. These CDP regions were found in proteins from all kingdoms of life, including viruses. However, eukaryotes had 1 order of magnitude more proteins containing long disordered regions than did archaea and bacteria. Sequence conservation in CDP regions varied, but was on average slightly lower than in regions of conserved order. In some cases, disordered regions evolve faster than ordered regions, in others they evolve slower, and in the rest they evolve at roughly the same rate. A variety of functions were found to be associated with domains containing conserved disorder. The most common were DNA/RNA binding, and protein binding. Many ribosomal proteins also were found to contain conserved disordered regions. Other functions identified included membrane translocation and amino acid storage for germination. Due to limitations of current knowledge as well as the methodology used for this work, it was not determined whether these functions were directly associated with the predicted disordered region. However, the functions associated with conserved disorder in this work are in agreement with the functions found in other studies to correlate to disordered regions. We have established that intrinsic disorder may be more common in bacterial and archaeal proteins than previously thought, but this disorder is likely to be used for different purposes than in eukaryotic proteins, as well as occurring in shorter stretches of protein. Regions of predicted disorder were found to be conserved within a large number of protein families and domains. Although many think of such conserved domains as being ordered, in fact a significant number of them contain regions of disorder that are likely to be crucial to their functions.

Figure 1

Histogram of PDB matches to CPD positions, by effective length

Figure 2

Histogram of PDB matches to CPD positions, by kingdom

Figure 3

Histogram of PDB matches to CPD positions, by member database

Figure 4

Graph of disorder prediction for eukaryotic proteins with domains containing the top five CPD regions: dentin matrix 1 protein family (A); fruit fly transformer family (B); N-terminal domain of aspartyl β-hydroxylase family (C); prion family (D); and E-MAP-115 family (E). The CPD regions are shown as horizontal black lines.

Figure 5

Graph of disorder prediction for bacterial proteins with domains containing the top five CPD regions: surface layer protein family (A); N-terminal of the translocated intimin receptor family (B); bacterial ribosomal protein L15 family (C); HrpZ family (D); the fertility inhibition protein family (E). The CPD region is shown as a black horizontal line.

Figure 6

Graph of disorder prediction for the viral proteins with domains containing the top five CPD regions: Ebola nucleoprotein family (A); minor capsid protein VI family (B); T-cell surface antigen CD2 (C). The CPD regions are shown as black horizontal lines.

Figure 7

Graph of disorder prediction for DNA topoisomerase, type II. The CPD region is shown as a black horizontal line.