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

Autor: Barbera S; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena 53100, Italy; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Rudbeck Laboratory, Uppsala SE-75185, Sweden., Raucci L; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena 53100, Italy., Tassone G; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena 53100, Italy., Tinti L; Toscana Life Sciences Foundation, Siena 53100, Italy., Prischi F; School of Life Sciences, University of Essex, Colchester CO4 3SQ, United Kingdom., Santucci A; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena 53100, Italy., Mongiat M; Department of Research and Diagnosis, Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano 33081, Italy., Tosi GM; Department of Medicine, Surgery and Neuroscience, Ophthalmology Unit, University of Siena, Siena, 53100, Italy., Galvagni F; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena 53100, Italy., Dimberg A; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Rudbeck Laboratory, Uppsala SE-75185, Sweden., Pozzi C; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena 53100, Italy. Electronic address: cecilia.pozzi@unisi.it., Orlandini M; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena 53100, Italy. Electronic address: maurizio.orlandini@unisi.it.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2023 Jan 01; Vol. 224, pp. 453-464. Date of Electronic Publication: 2022 Oct 18.
DOI: 10.1016/j.ijbiomac.2022.10.136
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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