This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: New research shows how artificial intelligence, combined with advanced experimental science, can help find "hidden" and unexplored proteins in the human body and reveal what they actually do, according to a new study published in Nature. The discovery suggests a new way to study how cells communicate, survive stress and possibly contribute to disease.
Researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, used AI to compare the shapes of more than 214 million predicted proteins. Instead of looking only at genetic sequences, they searched by three-dimensional form and found hidden members of the G protein-coupled receptor, or GPCR, family, a group that helps cells sense and respond to extracellular signals. "For decades, we have largely explored protein biology using sequence as our guide," said study senior author Daniel G.
Isom, Ph.D., a Sylvester researcher and faculty member in the Molecular and Cellular Pharmacology Department. "We wanted to know what biology we might be missing if we searched by three-dimensional structure instead. What we found suggests there is another layer of biology that has been hiding in plain sight." One protein in particular, TM184C, attracted their attention.
TM184C looks like a GPCR, but the research team noted that it behaved differently. Much of it was found inside the cell, within the membranes of intracellular vesicles, tiny packages that carry materials. They found that these vesicles traveled along microtubules, the cell's internal highways, and gathered in thin projections that connect neighboring cells.
Those projections act like bridges. Through them, cells exchange metabolites, vesicles and organelles, including mitochondria, which produce the energy that powers cells. When researchers disrupted TM184C, cells formed fewer connections and showed changes in shape and vesicle organization, suggesting TM184C helps build and manage these intercellular conduits.
"When we saw TM184C-positive vesicles moving through connections between cells, we realized these structures could be routes for substantial material exchange," said Jenniffer Arcuri, Ph.D., a senior scientist with Sylvester and lead author. "That completely changed how we thought about TM184C and made us consider how cells might use these connections to cooperate and compete for resources." The discovery raises a basic question: When cells share resources, who benefits? In healthy tissue, this exchange may help cells survive stress by moving fuel or damaged components where they are needed.
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