Tuesday 2 August 2011

Take your partner by the hand: a map of protein interactions in plants

A global consortium of scientists have established the first large-scale map of protein-protein interactions in the model plant Arabidopsis thaliana. The findings are reported in two papers in the 29th of July issue of Science. Using the yeast-two-hybrid technique, The Arabidopsis Interactome Consortium, exhaustively catalogued binary interactions between 8000 proteins (about 30% of the proteins encoded in the Arabidopsis genome). It was established that there were 6,200 interactions between 2,700 proteins.

Protein-protein ‘interactomes’ of bacteria, yeast and a few animals have revealed that proteins do not work alone. Almost all proteins physically interact with other proteins and this is thought to be important for controlling and modulating their function. The production of an interactome map for a plant is an important step in understanding the function of proteins that may have relevance for agriculture. A large fraction of the Arabidopsis genome encodes proteins of unknown function and working out what these proteins do is critical for a full understanding of the biology of the model plant. It is also an extreme challenge. Most of these proteins contain no clues in their sequence or predicted structure that might tell us what they do. Researchers are faced with a blank canvas of endless possibilities and such proteins tend not to get worked on because they are too ‘hard’ or the problem is too risky. An interactome map can help assign function to unknown proteins by using the ‘guilt by association’ principle. In the Arabidopsis interactome, it was found that proteins of similar function are more likely to interact with each other than those of different function. If proteins of unknown function are included in a particular interacting ‘community’ this makes it likely that they are part of the same biological process and helps guide research into their function.

An interaction maps also provides a topology that hypotheses can be tested against; the degree of interaction amongst proteins is not uniform - some proteins interact with more partners than others. These constitute ‘hubs’ in the functional interaction network and may be considered to more important for maintaining function. In a companion paper by Mukhtar et al this topological information was used to understand basic features of plant immunity against pathogens. Both bacterial and fungal pathogens secrete effector proteins into host plant cells that act to disable the plant defences. It was hypothesised that the effectors are more likely to disable hub proteins than those that are only weakly connected and this was confirmed by the interactome map that included pathogen effectors. Moreover, it was found that, despite being separated by 2 billion years of evolution, both the bacterial and fungal pathogens targeted the same hubs, providing important information that could be used to make broad-spectrum treatments for crop diseases.

Protein interactome maps take us a step beyond the genome, revealing aspects of biological function that are not accessible from gene sequence alone. "This starts to give us a big, systems-level picture of howArabidopsis works, and much of that systems-level picture is going to be relevant to--and guide further research on--other plant species, including those used in human agriculture and even pharmaceuticals," says Salk Institute biologist Joseph Ecker, a senior member of the Consortium.

Much remains to be done though, with the consortium estimating that the current interaction map only covers 2% of the possible 300,000 interactions that occur in Arabidopsis.

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