Perfect proteins preferred
Nature chooses well-ordered protein assembly, study finds
Researchers at the EMBL-European Bioinformatics Institute (EMBL-EBI), the Medical Research Council (MRC) and the University of Oxford in the UK have shown that the specific order in which proteins assemble into complexes is extremely important to how they function. Their findings, published in the journal Cell, shed light on an important question in evolution.
If humans and flies have around the same number of genes, how does one end up peeling a banana and the other hovering over it? The answer is in proteins: the complexity of an organism depends on its ability to form assemblies of proteins known as complexes, which in turn go on to perform any number of functions. The instructions for making a protein, contained in a gene, specify its sequence, shape and – importantly – its ability to interact with other proteins and thus form a protein complex.
Joseph Marsh, from EMBL-EBI, explains “We found a way to predict the order in which the individual subunits assemble into larger complexes, based on their three-dimensional structures”. This prediction principle was investigated by Helena Hernández and Zoe Hall, in the group of Dame Carol Robinson FRS at the University of Oxford, who used cutting-edge mass spectrometry techniques to observe the order in which several protein complexes assemble and disassemble in solution.
Searching through the sequenced genomes of many different organisms, the researchers were able to pinpoint ‘gene fusion’ events, in which the instructions for making two different proteins are permanently linked so they can create one large protein. These fusion events take place over millions of years of evolution, and only certain fusions that conserve the pathways have been selected for, while others have been discarded. This supports the finding that there is one main pathway by which each complex assembles.
“We’ve shown that in the rather messy process of evolution, well-ordered protein complexes get preferential treatment,” explains Joseph Marsh. “Nature goes to great lengths to conserve these assemblies – the genes involved actually modify themselves so that they can keep making proteins that fit together in a specific order.”
“It is simply fascinating to see that evolution actually acts at the level of assembly pathways – that the order in which proteins are assembled is so important,” adds Sarah Teichmann, from EMBL-EBI. “Putting together many different types of experimental data, we can begin to see a clearer picture of how complexity is introduced.”
Protein complexes are under evolutionary selection to assemble via ordered pathways -Marsh, J.A., et al. (2013) - Published online in Cell on 11 April - doi:10.1016/j.cell.2013.02.044