Fluorescence imaging of C. elegans fed with a new chemical probe developed in this study: a branched-chain fatty acid analogue. The red signal comes from a selective “click chemistry” reaction between the probe and a red fluorescent dye. Credit: Schroeder Lab/Boyce Thompson Institute
In a world where the intricacies of molecular biology often seem as vast and mysterious as the cosmos, a new study looks into the microscopic world of proteins, revealing a fascinating aspect of their existence. This revelation could have profound implications for the understanding and treatment of myriad human diseases.
Think of proteins as tiny motors driving the machinery of life. Just as engines require modifications to optimize their performance, proteins undergo “protein modification,” a crucial process changing their function, location, and lifespan. A key player in this modification process is the binding of proteins and fatty acids (“protein fatty acylation”), which is akin to the addition of a specialized component (i.e. fatty acids ) which allows proteins to anchor to cell membranes.
Through meticulous investigation using high-resolution mass spectrometry, scientists at the Boyce Thompson Institute (BTI) have discovered critical patterns of fatty acid binding in the model organism C. elegans, a microscopic worm that provides a window into fundamental biological processes.
Researchers, harnessing the power of “click chemistry” – a technique awarded two Nobel Prizes in Chemistry – have successfully mapped how different amino acids found in proteins are specifically modified with various fatty acids. Their work is published in the journal Proceedings of the National Academy of Sciences.
“We were surprised to find that different amino acids are modified by fatty acids from distinct biosynthetic pathways,” wrote Frank Schroeder, a professor at BTI and lead author of the study. “This unexpected finding highlights the link between protein modification and fat-specific metabolic pathways. It also provides the basis for further research into how protein function is affected by different fatty acids and their metabolism. “
The study, titled “Amino acid and protein specificity of protein fatty acylation in C. elegans,” isn’t just about understanding the inner workings of a small worm. The implications are broad and profoundly relevant to human health. The binding of proteins and fatty acids is a critical factor in diseases ranging from cancer to neurodegeneration, cardiovascular disorders and even infectious diseases.
“What we learn from C. elegans contributes significantly to our fundamental understanding of this type of protein modification,” said Bingsen Zhang, a graduate student in the Schroeder lab and first author of the study. “The more we understand about protein modification and function, the better we understand its central role in human health and disease.”
Additionally, the study reveals the first example of abundant modification of proteins with branched-chain fatty acids – a finding that could have parallels in higher animals and humans, given their presence in our diet and their production by intestinal microbiomes. The link between diet, gut health and protein modification could open new avenues in nutritional science.
Ultimately, this study is about the fundamental processes that keep every creature alive, from microscopic worms to humans. So the next time you see a worm, give a nod to biology’s unlikely hero and the scientists who uncover its secrets. Because sometimes the key to life’s greatest mysteries lies in its smallest inhabitants.
More information:
Bingsen Zhang et al, Amino acid and protein specificity of protein fatty acylation in C. elegans, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2307515121
Provided by the Boyce Thompson Institute
Quote: Small worm, no giant step: discovery of the highly specific attachment of fatty acids to proteins (January 22, 2024) retrieved on January 22, 2024 from
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