Bioinformatics Approaches to Predict Mutation Effects in the Binding Site of the Proangiogenic Molecule CD93

Abstract

The transmembrane glycoprotein CD93 has been identified as a potential new target to inhibit tumor angiogenesis. Recently, Multimerin-2 (MMRN2), a pan-endothelial extracellular matrix protein, has been identified as a ligand for CD93, but the interaction mechanism between these two proteins is yet to be studied. In this article, we aim to investigate the structural and functional effects of induced mutations on the binding domain of CD93 to MMRN2. Starting from experimental data, we assessed how specific mutations in the C-type lectin-like domain (CTLD) affect the binding interaction profile. We described a four-step workflow in order to predict the effects of variations on the inter-residue interaction network at the PPI, based on evolutionary information, complex network metrics, and energetic affinity. We showed that the application of computational approaches, combined with experimental data, allowed us to gain more in-depth molecular insights into the CD93–MMRN2 interaction, offering a platform for developing innovative therapeutics able to target these molecules and block their interaction. This comprehensive molecular insight might prove useful in drug design in cancer therapy.

CD93 regulates breast cancer growth and vasculogenic mimicry through the PI3K/AKT/SP2 signaling pathway activated by integrin β1

“…As a panendothelial extracellular matrix protein, MMRN2 can interact with CD93, and endothelial cell migration and angiogenesis in vitro can be impaired by disruption of the CD93–MMRN2 interaction. [ 25 ] Therefore, the influence of CD93 binding to MMRN2 on proliferation, migration, and vasculogenic mimicry was examined in MDA‐MB‐231 cells. Because MMRN2 is a specific ligand for CD93, we first verified this interaction by coimmunoprecipitation.…”

“…interaction. [25] Therefore, the influence of CD93 binding to MMRN2 on proliferation, migration, and vasculogenic mimicry was examined in MDA-MB-231 cells. Because MMRN2 is a specific ligand for CD93, we first verified this interaction by coimmunoprecipitation.…”