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Involvement of loops 2 and 3 of α-sarcin on its ribotoxic activity.
- Source :
-
Toxicon : official journal of the International Society on Toxinology [Toxicon] 2015 Mar; Vol. 96, pp. 1-9. Date of Electronic Publication: 2015 Jan 15. - Publication Year :
- 2015
-
Abstract
- Ribotoxins are a family of fungal ribosome-inactivating proteins displaying highly specific ribonucleolytic activity against the sarcin/ricin loop (SRL) of the larger rRNA, with α-sarcin as its best-characterized member. Their toxicity arises from the combination of this activity with their ability to cross cell membranes. The involvement of α-sarcin's loops 2 and 3 in SRL and ribosomal proteins recognition, as well as in the ribotoxin-lipid interactions involving cell penetration, has been suggested some time ago. In the work presented now different mutants have been prepared in order to study the role of these loops in their ribonucleolytic and lipid-interacting properties. The results obtained confirm that loop 3 residues Lys 111, 112, and 114 are key actors of the specific recognition of the SRL. In addition, it is also shown that Lys 114 and Tyr 48 conform a network of interactions which is essential for the catalysis. Lipid-interaction studies show that this Lys-rich region is indeed involved in the phospholipids recognition needed to cross cell membranes. Loop 2 is shown to be responsible for the conformational change which exposes the region establishing hydrophobic interactions with the membrane inner leaflets and eases penetration of ribotoxins target cells.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Absorption, Physicochemical
Amino Acid Sequence
Animals
Catalysis
Cell Line
Circular Dichroism
Cloning, Molecular
DNA, Complementary genetics
Endoribonucleases genetics
Escherichia coli
Fungal Proteins genetics
Molecular Sequence Data
Mutagenesis
Oligonucleotides genetics
Phospholipids metabolism
Protein Binding
Protein Conformation
Sequence Alignment
Spectrophotometry
Spodoptera
Endoribonucleases chemistry
Endoribonucleases toxicity
Fungal Proteins chemistry
Fungal Proteins toxicity
Models, Molecular
Protein Synthesis Inhibitors toxicity
Ribosomes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3150
- Volume :
- 96
- Database :
- MEDLINE
- Journal :
- Toxicon : official journal of the International Society on Toxinology
- Publication Type :
- Academic Journal
- Accession number :
- 25598497
- Full Text :
- https://doi.org/10.1016/j.toxicon.2015.01.007