From Protein Structure to Function with Bioinformatics.pdf

308 I.A. Cymerman et al.A recent example showed how function suggested by the fold of an ab initiomodel could be supported by other analyses (Rigden and Galperin 2008). TheSpoVS protein is known as being required for sporulation in sporulating bacteria,but in fact has a wider distribution. The phenotypic characterisation of SpoVSmutants says very little about its molecular role. However, the top models producedby both ROSETTA and I-TASSER matched well to the fold of the Alba archaealchromatin protein (Fig. 12.3a). This fold is strongly associated with nucleic acidbinding in various contexts and, furthermore, mapping electrostatic potential on tothe models revealed the pronounced positively-charged region characteristic ofnucleic acid binding proteins (Fig. 12.3b; see Chapter 7). Taken together theseanalyses suggest that SpoVS is a novel transcription factor that contributes to thecontrol of intricate gene expression patterns involved in sporulation (Rigden andGalperin 2008).A recent, large scale application of ab initio modelling, in a pipeline also involvingPSI-BLAST and threading-based structure predictions, analysed the yeastgenome (Malmstrom et al. 2007). The authors used a novel strategy to use knownfunctional information to help pick out correct putative structure-based matches ofab initio models to SCOP superfamilies. To this end, in addition to structural comparisons,the overlap of Gene Ontology (GO) terms between the target protein andproteins of the superfamily in question was assessed. These complementary sourcesof information were combined using Bayesian statistics. Figure 12.4 shows anFig. 12.3 Analysis of template free models of SpoVS suggests a nucleic acid-binding function(Rigden and Galperin 2008). (a) Both ROSETTA (grey) and I-TASSER (black) models of SpoVSare strongly similar to the structure of Alba, an archaeal chromatin protein (PDB code 1nfj;coloured in a spectrum from blue N-terminus to red C-terminus). (b) The electrostatic potential ofa putative SpoVS dimer, based on the ROSETTA model, with blue showing positive regions andred negative regions