Technical Highlight - September 2014
Short description: A search engine identifies assemblies with structural similarities, providing biologically relevant insights not accessible by comparison of individual proteins.
Much like peptides without sequence similarity can fold into almost identical tertiary structures, very dissimilar subunits can assemble into multiprotein complexes with high structural similarity. Since complexes carry out biological functions in cells, identifying similarities among assemblies can provide insights about function. Wiederstein and colleagues previously developed TopSearch, a tool for pairwise comparison of complexes, and have recently broadened its reach to query against all known biological assemblies in the PDB.
In a proof-of-concept analysis, the authors queried a newly determined structure of a homohexameric complex of unknown function from Salmonella typhimurium, which yielded a hit list of assemblies with a wide distribution of structure similarity scores (S). Top-ranked hits included proteins from the bacterial secretory system, with the highest scorer (S = 292.2) being the Pseudomonas aeruginosa homohexameric secretory protein Hcp3. Importantly, a search of the monomer failed to identify this similarity: S for Hcp3 was just 56.7, well below the threshold cutoff, which would not have allowed its identification as a match.
This tool can also be used for a comparative analysis of structures. For example, a query of a bacterial DNA clamp returned evolutionarily similar bacterial proteins as top hits, but what followed was a mix of eukaryotic and archaeal clamps. The authors suggest that these results reveal greater structural similarity among those groups, which are both homotrimers, versus the dimeric bacterial versions.
TopSearch is regularly updated with new data from the PDB. A query may be a PDB ID, or coordinates in PDB format can be used for data that have not been publicly released.
M. Wiederstein et al. Structure-Based Characterization of Multiprotein Complexes.
Structure. 22, 1063-1070 (2014). doi:10.1016/j.str.2014.05.005