University of California San Diego Researchers Use AlphaFold 3 to Decode Dual Signaling Receptor for Vascular Health

UC San Diego researchers use AI to find how the PAR1 receptor switches between healing and harming blood vessels, offering new hope for sepsis and stroke treatment.

By: AXL Media

Published: Mar 10, 2026, 11:41 AM EDT

Source: The information in this article was sourced from University of California - San Diego

The Molecular Switch Governing Vascular Integrity

A specialized protein sitting on the surface of blood vessel linings, known as protease-activated receptor-1 (PAR1), has long puzzled scientists due to its ability to trigger two diametrically opposed biological responses. Research led by the University of California San Diego has finally mapped the signaling pathways that allow this single receptor to either safeguard or destabilize the structural integrity of the vascular system. This breakthrough provides a critical understanding of how the body manages internal inflammation and could revolutionize the treatment of conditions defined by vascular leakage.

Decoding the Dual Role of the GRK5 Enzyme

The study reveals that the key to PAR1's behavior lies in the location of an intermediate enzyme called GRK5. When GRK5 is anchored to the cell's plasma membrane, it facilitates a protective response that counteracts inflammation and strengthens the blood vessel wall. Conversely, when the enzyme operates from within the fluid cytoplasm of the cell, it orchestrates a harmful inflammatory reaction. According to corresponding author JoAnn Trejo, PhD, this spatial distinction explains how the same molecular components can send such drastically different messages to the vascular system.

AI Modeling Reveals Structural Transformation Triggers

To visualize these complex interactions, the research team employed AlphaFold 3, a Nobel Prize winning artificial intelligence tool. The AI models demonstrated that the specific way the PAR1 receptor is chemically cut on its exterior determines its internal behavior. Depending on which enzyme performs the initial cut, the receptor changes shape to interact with GRK5 in specific cellular zones. This high-resolution modeling has allowed researchers to see for the first time how a single molecule can be "reprogrammed" by external stimuli to serve two different masters.