Photosynthesis group awarded major new BBSRC grant to investigate bioenergetic supercomplexes
Professor Matt Johnson has been awarded £1,057,000 from the Biotechnology and Biological Sciences Research Council (BBSRC) for a three-year project entitled "Do bioenergetic supercomplexes promote electron transfer by enhancing binding and turnover of electron carrier proteins?"
Explaining the context of the new grant Matt said: "Almost all life on Earth depends on electron transfer reactions taking place within the specialised energy-converting membranes of mitochondria, chloroplasts and bacteria. These reactions involve fleeting encounters between small, mobile electron-carrier proteins and the very large multi-subunit complexes embedded in these membranes. A long-standing puzzle in bioenergetics is why nature so often groups these large complexes into still larger assemblies known as 'supercomplexes'. Organisms unable to form supercomplexes show reduced fitness, and yet, despite decades of research, the functional advantage that supercomplexes provide has remained elusive."
"Traditional ensemble methods for studying these reactions average over the behaviour of millions of molecules at once and so cannot resolve the brief individual interactions that precede successful electron transfer. To get around this we have developed a single-molecule atomic force microscopy approach that allows us to watch the interactions between an electron-carrier protein and its target complex one encounter at a time. Our recent work, published in the Journal of the American Chemical Society, showed that this method can separate the short-lived 'encounter complex', which forms first through electrostatic attraction, from the longer-lived 'fully bound' state in which electron transfer takes place. Strikingly, our data suggest that supercomplexes work by enlarging the 'landing area' available to mobile carriers, dramatically boosting the chance that a productive encounter will occur."
"The new grant will allow us to test this hypothesis across three very different systems: the respiratory supercomplexes of yeast mitochondria, the photosynthetic supercomplex between photosystem I and the NADH-like dehydrogenase complex from spinach chloroplasts, and the unusual respiratory supercomplexes of the hospital pathogen Pseudomonas aeruginosa. We will combine single-molecule force measurements with molecular dynamics simulations, targeted mutagenesis and ensemble kinetics to pinpoint the residues responsible for the effect. We will then test whether we can recreate the same advantages in artificial supercomplexes built by fusing proteins that do not normally associate, building on our recent CRISPR-engineered photosystem I–ferredoxin-NADP+ reductase chimera in Chlamydomonas, published last year in The Plant Cell."
"By revealing how supercomplexes accelerate the flow of electrons through the bioenergetic membranes that sustain almost all life on Earth, this work has the potential to inform efforts to improve crop productivity, to design new light-powered cell factories for the sustainable manufacture of biofuels and pharmaceuticals, and to identify new antibiotic targets in pathogenic bacteria whose respiratory machinery differs fundamentally from our own."
The project is a collaboration with Professor Peter Brzezinski (Stockholm University), Dr Justin Di Trani (McGill University) and Professor Abhishek Singharoy (Arizona State University).