Deriving evolutionary relationships based on structural comparisons.
Membrane coat proteins (MC) are indispensable for intracellular traffic (clathrin, COPI, and COPII vesicle coats) and they predominate in the eukaryotic endomembrane system. Amongst other, they are present in the nuclear pore complex (Nups), complexes associated with the intraflagellar transport and membrane-tethering complexes. Phylogenetics and comparative genomic analyses have suggested that MC proteins arose by duplication and divergence from the pre-existing trafficking machinery that was present in the Last Eukaryotic Common Ancestor (LECA). The “protocoatomer” hypothesis suggests that these proteins share a common ancestor based on structural information. However, the MC proteins show a large variety of sizes and shapes and display an extreme sequence divergence; that difficult the reconstruction of the evolutionary intermediate steps of the MC proteins with the current comparison tools based on structural and sequence alignments.
During this year, we have developed an efficient and fast aligner tool for comparison between proteins using structural information called MOMA (MOrphing & MAtching). The current approach can align and give local structural alignment between two protein structures using the geometry of their secondary structure only. Recently, we have developed a new method to evaluate the significance of the alignments to be able to establish evolutionary relationships based on structural comparisons. Finally, we hope that this tool will help to understand better how membrane coat proteins contributed to the emergence of the complexity in eukaryotic cells and tried to understand the evolutionary relationships that exist between these complexes.