Dimerization of the C-type lectin-like receptor CD93 promotes its binding to Multimerin-2 in endothelial cells

TY - JOUR

T1 - Dimerization of the C-type lectin-like receptor CD93 promotes its binding to Multimerin-2 in endothelial cells

AU - Barbera, Stefano

AU - Raucci, Luisa

AU - Tassone, Giusy

AU - Tinti, Laura

AU - Prischi, Filippo

AU - Santucci, Annalisa

AU - Mongiat, Maurizio

AU - Tosi, Gian Marco

AU - Galvagni, Federico

AU - Dimberg, Anna

AU - Pozzi, Cecilia

AU - Orlandini, Maurizio

N1 - Funding Information: We thank Dr. Wildriss Viranaicken for the generous gift of the pTIFA vector. This research was partially funded by MIUR, Grant Dipartimento di Eccellenza 2018-2022 (number L.232,11-12-16), AIRC (IG-23643), and Italian Ministero della Salute (RF-2028-12365425). We thank the University of Siena for its contribution in publishing this manuscript with the Gold Open Access option. Funding Information: We thank Dr. Wildriss Viranaicken for the generous gift of the pTIFA vector. This research was partially funded by MIUR , Grant Dipartimento di Eccellenza 2018-2022 (number L.232,11-12-16 ), AIRC ( IG-23643 ), and Italian Ministero della Salute ( RF-2028-12365425 ). We thank the University of Siena for its contribution in publishing this manuscript with the Gold Open Access option. Publisher Copyright: © 2022

PY - 2023/1/1

Y1 - 2023/1/1

N2 - Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pathways involved in the vascular remodeling. Here for the first time we show that in endothelial cells CD93 is structured as a dimer and that this oligomeric form is physiologically instrumental for the binding of CD93 to its ligand Multimerin-2. Crystallographic X-ray analysis of recombinant CD93 reveals the crucial role played by the C-type lectin-like and sushi-like domains in arranging as an antiparallel dimer to achieve a functional binding state, providing key information for the future design of new drugs able to hamper CD93 function in neovascular pathologies.

AB - Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pathways involved in the vascular remodeling. Here for the first time we show that in endothelial cells CD93 is structured as a dimer and that this oligomeric form is physiologically instrumental for the binding of CD93 to its ligand Multimerin-2. Crystallographic X-ray analysis of recombinant CD93 reveals the crucial role played by the C-type lectin-like and sushi-like domains in arranging as an antiparallel dimer to achieve a functional binding state, providing key information for the future design of new drugs able to hamper CD93 function in neovascular pathologies.

KW - Angiogenesis

KW - CD93

KW - Crystallography

KW - Mass spectrometry

KW - Neovascularization

UR - http://www.scopus.com/inward/record.url?scp=85140323562&partnerID=8YFLogxK

U2 - 10.1016/j.ijbiomac.2022.10.136

DO - 10.1016/j.ijbiomac.2022.10.136

M3 - Article

C2 - 36265539

AN - SCOPUS:85140323562

SN - 0141-8130

VL - 224

SP - 453

EP - 464

JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

ER -