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oai:uvadoc.uva.es:10324/654882024-02-01T20:02:03Zcom_10324_65189com_10324_954com_10324_894col_10324_65190

Iglesias Álvarez, María del Rosario Ferreras Rodríguez, José Miguel Di Maro, Antimo Citores González, Lucía 2024-02-01T08:30:01Z 2024-02-01T08:30:01Z 2018 Biochimica et Biophysica Acta (BBA) -General Subjects, March 2018, vol. 1862 (3), p. 460-473 0304-4165 https://uvadoc.uva.es/handle/10324/65488 10.1016/j.bbagen.2017.11.014 460 3 473 Biochimica et Biophysica Acta (BBA) - General Subjects 1862 Background: Sambucus ebulus is a rich source of ribosome-inactivating proteins (RIPs) and RIP-related lectins generated from multiple genes. These proteins differ in their structure, enzymatic activity and sugar binding specificity. Methods: We have purified and characterized ebulin-RP from S. ebulus leaves and determined the amino acid sequence by cDNA cloning. Cytotoxicity was studied in a variety of cancer cells and a comparative study of the ability of ebulin-RP to bind sugars using "in vitro" and "in silico" approaches was performed. Results: Ebulin-RP is a novel heterodimeric type 2 RIP present in S. ebulus leaves together with the type 2 RIP ebulin l, which displayed rRNA N-glycosidase activity but unlike ebulin l, lacked functional sugar binding domains. As a consequence of changes in its B-chain, ebulin-RP displayed lower cytotoxicity than ebulin l towards cancer cells and induced apoptosis as the predominant pattern of cell death. Conclusions: Ebulin-RP is a novel member of the ebulin gene family with low cytotoxicity as a result of deficient sugar binding domains. Type 2 RIP genes from Sambucus have evolved to render proteins with different sugar affinities that may be related to different biological activities and could result in an advantage for the plant. General significance: The ebulin family of RIPs and lectins can serve as a good model for studying the evolutionary process which may have occurred in RIPs. The lack of cytotoxicity of ebulin-RP makes it a good candidate as a toxic moiety in the construction of immunotoxins and conjugates directed against specific targets. eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ Copyright © 2017 Elsevier B.V. Attribution-NonCommercial-NoDerivatives 4.0 Internacional Ebulin-RP, a novel member of the Ebulin gene family with low cytotoxicity as a result of deficient sugar binding domains info:eu-repo/semantics/article