Lebecetin is an anticoagulant C-type lectin-like protein that was previously isolated from Macrovipera lebetina venom and described to consist of two subunits (alpha and beta). It was reported to potently prevent platelet aggregation by binding to glycoprotein Ib and to exhibit a broad spectrum of inhibitory activities on various integrin-mediated functions of tumor cells, including adhesion, proliferation, and cell migration. This study aimed to investigate the structure-function of lebecetin. Accordingly, the cDNA of each subunit was cloned and separately or jointly expressed in the human embryonic kidney cells using two vectors with different selectable tags. The immunofluorescence analysis of transfected cells revealed significant expression levels and co-localization of the two lebecetin subunits. The recombinant proteins were efficiently secreted and purified using metal-chelating affinity chromatography. We found that the Lebecetin alpha and beta subunits were produced as a mixture of homodimers and heterodimers and that the heterodimerization represents a prerequisite for functioning.
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http://dx.doi.org/10.1002/btpr.1632 | DOI Listing |
FASEB J
January 2025
Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, NHC Key Laboratory of Thrombosis and Hemostasis, The First Affiliated Hospital of Soochow University, Suzhou, China.
Acute liver failure (ALF) is a life-threatening condition that occurs when the liver sustains severe damage and rapidly loses its function. The primary cause of ALF is the overdose of acetaminophen (APAP), and its treatment is relatively limited. The involvement of the complement system in the development of ALF has been implicated.
View Article and Find Full Text PDFCells
December 2024
Division of Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach, Germany.
Membrane proteins, especially extracellular domains, are key therapeutic targets due to their role in cell communication and associations. Yet, their functions and interactions often remain unclear. This study presents a general method to discover interactions of membrane proteins with immune cells and subsequently to deorphanize their respective receptors.
View Article and Find Full Text PDFImmunol Rev
January 2025
W. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, Maryland, USA.
Natural killer (NK) cells are essential elements of the innate immune response against tumors and viral infections. NK cell activation is governed by NK cell receptors that recognize both cellular (self) and viral (non-self) ligands, including MHC, MHC-related, and non-MHC molecules. These diverse receptors belong to two distinct structural families, the C-type lectin superfamily and the immunoglobulin superfamily.
View Article and Find Full Text PDFSci Rep
December 2024
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Inoculation of Bothrops jararaca snake venom (BjV) induces thrombocytopenia in humans and various animal species. Although several BjV toxins acting on hemostasis have been well characterized in vitro, it is not known which one is responsible for inducing thrombocytopenia in vivo. In previous studies, we showed that BjV incubated with metalloproteinase or serine proteinase inhibitors and/or anti-botrocetin antibodies still induced thrombocytopenia in rats and mice.
View Article and Find Full Text PDFCell Commun Signal
December 2024
EV group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, Viikinkaari 9, Helsinki, 00790, Finland.
Background: Beyond their conventional roles in hemostasis and wound healing, platelets have been shown to facilitate hematogenous metastasis by interacting with cancer cells. Depending on the activation route, platelets also generate different platelet-derived extracellular vesicles (PEVs) that may educate cancer cells in the circulation or within the tumor microenvironment. We engaged different platelet-activating receptors, including glycoprotein VI and C-type lectin-like receptor 2, to generate a spectrum of PEV types.
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