8ivd

From Proteopedia

COMPLEX STRUCTURE OF CD93-IGFBP7

Structural highlights

8ivd is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.24Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IBP7_HUMAN Familial retinal arterial macroaneurysm. The disease is caused by variants affecting the gene represented in this entry.

Function

IBP7_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 PubMed

The 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

↑ Akaogi K, Okabe Y, Funahashi K, Yoshitake Y, Nishikawa K, Yasumitsu H, Umeda M, Miyazaki K. Cell adhesion activity of a 30-kDa major secreted protein from human bladder carcinoma cells. Biochem Biophys Res Commun. 1994 Feb 15;198(3):1046-53. PMID:8117260 doi:10.1006/bbrc.1994.1149
↑ Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG. Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. J Biol Chem. 1996 Nov 29;271(48):30322-5. PMID:8939990 doi:10.1074/jbc.271.48.30322
↑ Xu Y, Sun Y, Zhu Y, Song G. Structural insight into CD93 recognition by IGFBP7. Structure. 2024 Mar 7;32(3):282-291.e4. PMID:38218180 doi:10.1016/j.str.2023.12.011