Upgrading the world’s most important protein
The world’s most important protein is getting an upgrade. Despite it being the most abundant protein in the world, we are still getting to the roots of how Rubisco, the protein at the heart of photosynthesis, works.
As a critical component in the 3.5 billion-year-old photosynthesis process of bacteria, algae and plants, Rubisco is responsible for producing the energy-rich sugars that power life on earth and the oxygen-rich atmosphere we live in. Present in all photosynthetic organisms, Rubisco is truly central to life as we know it.
Yet for all its glorious benefits, it is curiously inefficient at its job. Within the photosynthesis process, Rubisco takes carbon dioxide from the air and, through a number of chemical steps, turns it into complex sugars that the plant – and those that eat it – then use for energy! Unfortunately, it is not selective enough in gathering carbon dioxide from the air around it, often picking up oxygen instead and wasting energy by producing unwanted by-products.
Professor Jill Gready from the Department of Genome Sciences within The Australian National University’s John Curtin School of Medical Research is working to understand and improve the functioning of the Rubisco protein. Producing a plant with a more efficient Rubisco promises to improve crops in groundbreaking ways. It could lead to increased plant growth, and thus increased yields from a single planting, or alternatively could make plants more resilient in the face of increasingly variable weather being experienced globally, and predicted to come from climate change.
Improving protein activity is no simple task, especially for one with a process as complicated as Rubisco. To understand the protein, Professor Gready and her team use quantum mechanical, molecular mechanical and molecular dynamical models, so called “QM/MM + MD” models, to describe the chemical-reaction steps and the influence of thousands of interactions of atoms within the Rubisco molecule on them, deducing how tiny changes to the structure from mutations might improve its efficiency.
To do this kind of modelling, the team have developed methods that use high-performance computing resources from NCI together with public DNA-sequence and x-ray crystal-structure data from decades of investigation by others into Rubisco. Simulating the workings of the protein in action, with all of the chemical energies and atomic interactions involved, requires in-depth knowledge of chemical, physical, biological and evolutionary processes.
Professor Gready says, “We are the only group in the world doing Rubisco modelling at this level of detail. The modelling feeds directly into our laboratory experiments and plant-growth trials. The results have led to licensing agreements and formation of a start-up company to commercialize and deliver improved crops to farmers over the next five to ten years.”
The images below show surface views of the crystal structure of Rubisco holoenzyme (L8S8) from spinach in complex with a reaction intermediate analogue shown in side (A) and top (B) views (down the hole in middle). Large subunits are shown in cyan and small subunits in white. MD simulations were carried out using two large (LA and LD) and two small (SI and SL) subunits, all highlighted in magenta colour. Atoms involved in the dynamic region of the simulation are shown in ball-and-stick model highlighted by a circle and labelled “Dynamic” in A. Atoms outside of this region were kept fixed during the simulation (region labelled “Frozen” in A).