RT info:eu-repo/semantics/article
T1 Ebulin-RP, a novel member of the Ebulin gene family with low cytotoxicity as a result of deficient sugar binding domains
A1 Iglesias Álvarez, María del Rosario
A1 Ferreras Rodríguez, José Miguel
A1 Di Maro, Antimo
A1 Citores González, Lucía
K1 Sambucus ebulus L.
K1 Lectin
K1 Ribosome-inactivating protein
K1 Ricin
K1 apoptosis
K1 RNA-N-glycosidase
K1 2302.27 Proteínas
K1 2302 Bioquímica
K1 2302.21 Biología Molecular
K1 2415.02 Biología Molecular de Plantas
AB 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.
PB Elsevier
SN 0304-4165
YR 2018
FD 2018
LK https://uvadoc.uva.es/handle/10324/65488
UL https://uvadoc.uva.es/handle/10324/65488
LA eng
NO Biochimica et Biophysica Acta (BBA) -General Subjects, March 2018,  vol. 1862 (3), p. 460-473
NO Producción Científica
DS UVaDOC
RD 22-nov-2024