Nav: Home

Interrogating proteins

May 22, 2017

This research will help to design small proteins and small molecules that could be the basis for future biotechnologies and medicines.

A team of chemists and biochemists from the Bristol BioDesign Institute have designed a new protein structure.

This is much simpler than most naturally occurring proteins, which has allowed the scientists to unpick some of the molecular forces that assemble and stabilise protein structures. The work is published in the journal Nature Chemical Biology.

Proteins are the workhorses of biology. For example, they help convert light energy into sugar in plants, transport oxygen from our lungs to our muscles, and combine sugar and oxygen to release energy to make the muscles work. To perform these tasks, proteins must adopt specific 3D structures, called protein folds.

In chemical terms, proteins are polymers, or strings of amino acids, much like the beads of a necklace. There are 20 different chemistries of the amino-acid building blocks. It is the combination of these along the protein string that determines how a protein folds up into its functional 3D shape. Despite decades of effort, scientists still don't understand how biology achieves this protein-folding process, or, once folded, how protein structures are stabilised.

To address this problem, the Bristol team have combined two types of protein structure--called an ? helix and a polyproline II helix--to make a stripped down, or simplified protein called a miniprotein.

This is basic science with the simple aim of seeing how small a stable protein structure can be. It is important, as natural proteins are usually very large and cumbersome structures, which are currently too complicated for chemists and biochemists to dissect and understand. In the miniprotein, which the team call 'PP?', the two helices wrap around each other and their amino acids contact intimately in what are termed 'knobs-into-holes' interactions. This was expected, indeed the team designed PP? from scratch based on their understanding of these interactions.

Dr Emily Baker, who led the research in Professor Dek Woolfson's laboratory, decided to change some of the amino acids in these knobs-into-holes interactions to non-natural amino acids, which the wonders of modern protein chemistry allow.

By doing this, Emily discovered that as well as the expected forces that hold proteins together, known as hydrophobic interactions, other more-subtle forces were at play in stabilising the miniprotein structure.

Chemists know these small forces as CH-? interactions, and they are found throughout the chemical world. When Drs Gail Bartlett and Kieran Hudson, also from the Bristol team, searched the thousands of natural protein structures available they found many examples of these CH-? interactions.

Moreover, the proteins that they occur in play roles in different biological process, many of which are associated with disease. This presents potential targets for new drugs, and the CH-? interactions may provide a valuable new route into developing these. Dr Baker explained: "Our work has implications not only for understanding the basic science of protein folding and stability, but also for guiding the design and engineering of new proteins and drug molecules."

Professor Woolfson added: "This is precisely what the new Bristol BioDesign Institute is about. We aim to deliver the very best basic science. In this way, we will open unforeseen routes to translating fundamental science into biotechnology and biomedical applications."
-end-
The work is a collaboration involving Dr Emily Baker, Dr Christopher Williams, Dr Kieran Hudson, Dr Gail Bartlett, Dr Jack Heal, Kathryn Porter Goff, Dr Richard Sessions, Professor Matthew Crump and Professor Dek Woolfson. It is funded by ERASynBio and BrisSynBio, the ERC, and the Wellcome Trust.

Paper:

'Engineering protein stability with atomic precision in a monomeric miniprotein' by E. Baker, C. Williams, K. Hudson, G. Bartlett, J. Heal, K. Porter Goff, R. Sessions, M. Crump and D. Woolfson in Nature Chemical Biology. The full paper is available online at DOI: 10.1038/nchembio.2380.

University of Bristol

Related Amino Acids Articles:

A unique amino acid for brain cancer therapy
Researchers discover potential application of amino acid taurine in photodynamic therapy for brain cancer.
Nickel: A greener route to fatty acids
Chemists designed a nickel catalyst that easily transforms petroleum feedstocks into valuable compounds like fatty acids.
Amino acids in diet could be key to starving cancer
Cutting out certain amino acids - the building blocks of proteins -- from the diet of mice slows tumor growth and prolongs survival, according to new research published in Nature.
How to brew high-value fatty acids with brewer's yeast
Researchers at Goethe University Frankfurt have succeeded in producing fatty acids in large quantities from sugar or waste containing sugar with the help of yeasts.
Diverse natural fatty acids follow 'Golden Mean'
Bioinformatics scientists at Friedrich Schiller University in Jena (Germany) have discovered that the number of theoretically possible fatty acids with the same chain length but different structures can be determined with the aid of the famous Fibonacci sequence.
Simple fats and amino acids to explain how life began
Life is a process that originated 3.5 billion years ago.
Newly revealed amino acid function could be used to boost antioxidant levels
A Japanese research team has become the first in the world to discover that 2-aminobutyric acid is closely involved in the metabolic regulation of the antioxidant glutathione, and that it can effectively raise levels of glutathione in the body when ingested.
An amino acid controls plants' breath
IBS plant scientists demonstrate that the amino acid L-methionine activates a calcium-channel regulating the opening and closing of tiny plant pores.
Genetic differences in amino acid metabolism are linked to a higher risk of diabetes
A study published today in the journal PLOS Medicine has identified the five genetic variants associated with higher levels of the branched-chain amino acids isoleucine, leucine and valine.
Withholding amino acid depletes blood stem cells, Stanford researchers say
A new study shows that a diet deficient in valine effectively depleted the blood stem cells in mice and made it possible to perform a blood stem cell transplantation on them.

Related Amino Acids Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".