Structural insight into CD93 recognition by IGFBP7

Yueming Xu; Yi Sun; Yuwen Zhu; Gaojie Song

doi:10.1016/j.str.2023.12.011

Structural insight into CD93 recognition by IGFBP7

Structure. 2024 Mar 7;32(3):282-291.e4. doi: 10.1016/j.str.2023.12.011. Epub 2024 Jan 12.

Authors

Yueming Xu¹, Yi Sun², Yuwen Zhu³, Gaojie Song⁴

Affiliations

¹ Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
² Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
³ Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: yuwen.zhu@cuanschutz.edu.
⁴ Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: gjsong@bio.ecnu.edu.cn.

PMID: 38218180
DOI: 10.1016/j.str.2023.12.011

Abstract

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 EGF₁ 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.

Keywords: CD93; EC angiogenesis; IGFBP7; crystal structure; tumor therapy.

MeSH terms

Animals
Endothelial Cells* / metabolism
Endothelial Cells* / pathology
Humans
Membrane Glycoproteins / metabolism
Mice
Neoplasms*
Receptors, Complement / metabolism
Signal Transduction
Tumor Microenvironment

Substances

Membrane Glycoproteins
Receptors, Complement
insulin-like growth factor binding protein-related protein 1
complement 1q receptor

Abstract

MeSH terms

Substances

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