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http://purl.uniprot.org/citations/37121976http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37121976http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.org/dc/terms/identifier"doi:10.1038/s12276-023-00992-4"xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Fu Y."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Lee D.S."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Kim H.M."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Yang J."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Kim D.K."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Yun J."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Han A.R."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Ryu J.K."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Suh J.K."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Yin G.N."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/author"Min K.W."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/name"Exp Mol Med"xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/pages"1013-1022"xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/title"Crystal structure of LRG1 and the functional significance of LRG1 glycan for LPHN2 activation."xsd:string
http://purl.uniprot.org/citations/37121976http://purl.uniprot.org/core/volume"55"xsd:string
http://purl.uniprot.org/citations/37121976http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37121976
http://purl.uniprot.org/citations/37121976http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/37121976
http://purl.uniprot.org/uniprot/#_A0A0G2JGM8-mappedCitation-37121976http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37121976
http://purl.uniprot.org/uniprot/#_P02750-mappedCitation-37121976http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37121976
http://purl.uniprot.org/uniprot/#_Q3UQ39-mappedCitation-37121976http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37121976
http://purl.uniprot.org/uniprot/#_Q0P6A0-mappedCitation-37121976http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/37121976