8ivd | pdb_00008ivd
COMPLEX STRUCTURE OF CD93-IGFBP7
Structural highlights
DiseaseIBP7_HUMAN Familial retinal arterial macroaneurysm. The disease is caused by variants affecting the gene represented in this entry. FunctionIBP7_HUMAN Binds IGF-I and IGF-II with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion.[1] [2] C1QR1_HUMAN Receptor (or element of a larger receptor complex) for C1q, mannose-binding lectin (MBL2) and pulmonary surfactant protein A (SPA). May mediate the enhancement of phagocytosis in monocytes and macrophages upon interaction with soluble defense collagens. May play a role in intercellular adhesion. Publication Abstract from PubMedThe CD93/IGFBP7 axis proteins are key factors expressed in endothelial cells (EC) that mediate EC angiogenesis and migration. Their upregulation contributes to tumor vascular abnormality and a blockade of this interaction promotes a favorable tumor microenvironment for therapeutic interventions. However, the interactions of these proteins with each other remain unclear. In this study, we determined a partial structure of the human CD93-IGFBP7 complex comprising the EGF(1) domain of CD93 and the IB domain of IGFBP7. Mutagenesis studies confirmed interactions and specificities. Cellular and mouse tumor studies demonstrated the physiological relevance of the CD93-IGFBP7 interaction in EC angiogenesis. Our study provides leads for the development of therapeutic agents to precisely disrupt unwanted CD93-IGFBP7 signaling in the tumor microenvironment. Additionally, analysis of the CD93 full-length architecture provides insights into how CD93 protrudes on the cell surface and forms a flexible platform for binding to IGFBP7 and other ligands. Structural insight into CD93 recognition by IGFBP7.,Xu Y, Sun Y, Zhu Y, Song G Structure. 2024 Mar 7;32(3):282-291.e4. doi: 10.1016/j.str.2023.12.011. Epub 2024 , Jan 12. PMID:38218180[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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