In using AI-powered tools to map proteins in the human gut microbiome, researchers have challenged the traditional view of the relationship between protein sequence, structure and function.
From growing our cells, tissues and organs to repairing our bodies as we age, proteins are responsible for nearly every task of cellular life. A central tenet in biology has long been that protein sequence dictates protein structure, and that structure dictates its function. But now, an international study led by scientists at the Flatiron Institute in New York City has revealed striking examples in which this tenet does not hold true. By applying robust prediction methods powered by artificial intelligence to proteins from the microbiome of the human gut, the researchers have uncovered many cases in which a protein’s sequence, structure and function do not line up as expected. These findings, published on April 26 in Nature Communications, hint at new mechanisms driving the unparalleled biodiversity of the gut microbiome. They also lay critical groundwork for deeper investigations into how our gut microbiome may impact our health.
“This work changes how we think about protein structure and function,” says Julia Koehler Leman, a project leader and research scientist at the Flatiron Institute’s Center for Computational Biology (CCB) and one of the study’s lead authors. “We see a broader range of sequences and functions associated with a smaller set of structures, which suggests more complex factors behind protein function.”