A multinational research team led by researchers at Institute of Science Tokyo, RIKEN, and the University of Toronto has revealed how a tryptophan-rich allosteric communication network regulates receptor dynamics and activation of the human adenosine A_2A receptor (A_2AR), a major G protein-coupled receptor (GPCR) drug target. By integrating experimental functional assays and residue-specific NMR with molecular simulations and fast allostery-prediction algorithms based on rigidity theory, the team mapped long-range allosteric communication pathways linking the ligand-binding pocket to the intracellular G protein–coupling machinery and identified a central role for tryptophan residues along these pathways. The study also clarifies the functional role of the receptor’s conserved sodium-binding pocket, showing that sodium egress strongly promotes activation-related conformational states, including a precoupled state that likely prepares the receptor for productive G protein interaction. These findings deepen our understanding of GPCR activation and allostery, and may support future development of allosteric GPCR drugs.

Beyond the specific mechanism, this work addresses a major bottleneck for AI in structural biology: recent advances such as AlphaFold have transformed prediction of static protein structures, but AI still cannot reliably predict the dynamics and allosteric communication that determine function, signaling, and drug response. To help close this gap, the researchers developed and applied fast computational methods for probing allosteric and dynamic regulation in protein structures and anchored these predictions with experimental NMR validation. The resulting experimentally validated, computationally generated data on allostery and dynamics—and a scalable approach to extend these datasets across diverse receptors and conditions—provide scarce, high-value training and benchmarking data for next-generation AI models aimed at predicting protein function beyond static structure, accelerating future AI-driven prediction of protein function and the design of selective GPCR therapeutics.

Fibrotic scarring is a major challenge in recovery post spinal cord injury (SCI). Researchers reveal that transforming growth factor- β1 (TGF- β1) signaling promotes scar tissue formation by encouraging fibroblast development from MSCs and pericytes. Using a mouse model, Dr. Dayu Pan and his team of researchers reveal that limiting macrophage-derived TGF-β1 reduced scar formation and improved recovery, suggesting that targeting abnormal TGF- β1 activation may aid in recovery after SCI.

Glycosylated RNAs (glycoRNA) represent a newly discovered class of glycosylated biomolecules that challenge the long-standing view that glycosylated occurs exclusively on proteins and lipids. Accumulating evidence indicates that glycoRNA are widely distributed across diverse cell types and species and participate in biological process such as immune regulation and intercellular communication. In glycoRNA research, mass spectrometry (MS)-based glycomics provides critical information, offering insights into the biological functions of RNA glycosylation. This review summarizes recent advances in MS-based analytical strategies, including sample collection, RNA extraction, glycoRNA enrichment, glycan release and purification, derivatization, liquid chromatography separation, MS detection, and data analysis.

Nicotinamide mononucleotide (NMN) confers broad-spectrum resistance in plants, offering a simple, environmental-friendly, and promising strategy for safeguarding crops against diverse phytopathogens. These findings also provide valuable insights for future in-depth studies into the functional mechanisms of NMN.

The human brain develops through an intricate balance of cellular growth, connectivity, and metabolism. A new study reveals that a single metabolic enzyme, glutamine synthetase (GS), plays a decisive role in shaping brain circuits after birth by directing astrocyte maturation and neuronal connectivity in the cerebral cortex.

A new 3D model reveals how mosquitoes adjust their flight patterns in response to visual and chemical cues. The research could help in the design of more effective traps and mosquito control strategies.

Two researchers at the University of Zurich have discovered and described a new, previously unknown palm species found in the virgin forests of Colombia. In close cooperation with an indigenous community there, they mapped the geographical distribution of the palm species and subjected their study to a local peer review process.