Introduction: A New Bridge Between Energy Metabolism and Immunity
Cell recently published a groundbreaking study from the Hui Zheng Lab (Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China) titled " Pyruvate is a natural suppressor of interferon signaling by inducing STAT1 protein pyruvylation."This research identifies a brand-new protein post-translational modification (PTM)—Lysine Pyruvylation (Pyru)—for the first time, revealing a novel mechanism by which the metabolic intermediate pyruvate regulates antiviral immunity.
Scientific Challenge: The Mystery of Pyruvate's Non-metabolic Functions
As the core product of the glycolysis pathway, pyruvate's role in energy metabolism is well-established. However, whether pyruvate can directly exert non-metabolic regulatory functions through PTMs—much like its downstream metabolite lactate (lactylation)—has long been a significant gap in the life sciences. Bridging this missing link is crucial for understanding how high-glucose environments weaken human immunity.
Technical Roadmap: PTM BIO Empowering the "Identification" of a Novel Modification
The precise identification of this novel modification was the primary challenge of this study due to its unique chemical properties and the difficulty of capturing modified sites. PTM BIO leveraged its leading expertise in novel acylation proteomics to provide decisive support for this research:
Mass Spectrometry Analysis: By combining biotin-labeled pyruvate with PTM BIO’s high-resolution mass spectrometry platform, the research team identified a mass shift of 70.0468 Da at the Lysine 201 site of the STAT1 protein for the first time, confirming the existence of the Pyruvylation (Pyru) modification.
Custom Antibody Development: Based on the MS discovery, PTM BIO developed a site-specific pyruvylation antibody (STAT1-K201Pyru) for the team. This critical tool enabled researchers to verify the prevalence and independence of this modification across cellular, animal, and clinical samples.
Core Discovery: STAT1 Pyruvylation Suppresses Antiviral Immunity
The study reveals that under high-glucose conditions, the elevated levels of pyruvate generated by glycolysis induce K201 pyruvylation of STAT1.
The Mechanism: This pyruvylation modification directly hinders the interaction between STAT1 and STAT2, effectively "silencing" the Type I Interferon (IFN-I) signaling pathway.
Clinical Relevance: Analysis of human peripheral blood samples showed that patients with hyperglycemia exhibit higher serum pyruvate levels and significantly enhanced STAT1 pyruvylation, providing a molecular explanation for the weakened antiviral capacity in populations with metabolic abnormalities.
PTM BIO: Leading the Discovery and Validation of Novel Protein Modifications
PTM BIO is honored to have provided the foundational technology for this landmark discovery. As a pioneer in the field of novel acylation research, PTM BIO remains at the industry forefront. We have not only helped clients establish the detection paradigm for Pyruvylation, but also offer comprehensive solutions for various novel modifications including Lactylation, Propionylation, and Succinylation.
We provide end-to-end services, from high-depth PTM proteomics screening to site-specific custom antibody validation, helping researchers tackle complex mechanistic questions and accelerate the publication of high-impact studies in leading journals such as Cell, Nature, and Science.
Explore more cutting-edge research tools and access our list of novel acylation antibodies:
