ArticleExperimental & molecular medicine2023
Crystal structure of LRG1 and the functional significance of LRG1 glycan for LPHN2 activation.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- GALNT6-glycosylated LRG1 mediates the interaction between M2 macrophages and pancreatic cancer cells by activating CCR1/PI3K/AKT axis.Molecular and cellular biochemistry · 2026Article
- LRG1 as a Potential Therapeutic Target in Atherosclerosis: Mechanistic Basis and Current Evidence.Cells · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Review
- High-dose SFRP2 attenuates fibrosis and promotes angiogenesis via Wnt signaling modulation in diabetic erectile dysfunction.Open life sciences · 2026Article
- Aerobic Exercise-Induced TGF-β Receptor Reprogramming Disrupts Neutrophil-Microglia Crosstalk to Attenuate Early Brain Injury after Subarachnoid Hemorrhage.Research (Washington, D.C.) · 2026Article
- Integrative transcriptomic and genomic insights into diabetic kidney disease: evidence from multi-omics analysis and experimental validation.Renal failure · 2025Article
- Evolutionary and Functional Insights of Leucine-Rich Alpha-2-Glycoprotein 1 in Cetacean Wound Healing: The First Identification of LRG1 in the Bottlenose Dolphin (Tursiops truncatus).Journal of experimental zoology. Part B, Molecular and developmental evolution · 2025Article
- The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Gut Feeling: Biomarkers and Biosensors' Potential in Revolutionizing Inflammatory Bowel Disease (IBD) Diagnosis and Prognosis-A Comprehensive Review.Biosensors · 2025Review
- Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repair.iScience · 2025Article
- Exploration of Leucine-Rich Alpha-2 Glycoprotein 1 (LRG1) and Its Association with Proangiogenic Mediators in Sickle Cell Disease: A Potential Player in the Pathogenesis of the DiseaseTurkish journal of haematology : official journal of Turkish Society of Haematology · 2025Article
- MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2.Experimental & molecular medicine · 2025Article
- Single-cell RNA sequencing unveils Lrg1's role in cerebral ischemia‒reperfusion injury by modulating various cells.Journal of neuroinflammation · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1), primarily produced by hepatocytes and neutrophils, is a multifunctional protein that modulates various signaling cascades, mainly TGFβ signaling. Serum LRG1 and neutrophil-derived LRG1 have different molecular weights due to differences in glycosylation, but the impact of the differential glycan composition in LRG1 on its cellular function is largely unknown. We previously reported that LRG1 can promote both angiogenic and neurotrophic processes under hyperglycemic conditions by interacting with LPHN2. Here, we determined the crystal structure of LRG1, identifying the horseshoe-like solenoid structure of LRG1 and its four N-glycosylation sites. In addition, our biochemical and cell-biological analyses found that the deglycosylation of LRG1, particularly the removal of glycans on N325, is critical for the high-affinity binding of LRG1 to LPHN2 and thus promotes LRG1/LPHN2-mediated angiogenic and neurotrophic processes in mouse tissue explants, even under normal glucose conditions. Moreover, the intracavernous administration of deglycosylated LRG1 in a diabetic mouse model ameliorated vascular and neurological abnormalities and restored erectile function. Collectively, these data indicate a novel role of LRG1 glycans as molecular switches that can tune the range of LRG1's cellular functions, particularly the LRG1/LPHN2 signaling axis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.