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A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells
- Source :
- Nucleic Acids Research
- Publication Year :
- 2010
- Publisher :
- Oxford University Press, 2010.
-
Abstract
- Maize ribosome-inactivating protein (RIP) is a plant toxin that inactivates eukaryotic ribosomes by depurinating a specific adenine residue at the α-sarcin/ricin loop of 28S rRNA. Maize RIP is first produced as a proenzyme with a 25-amino acid internal inactivation region on the protein surface. During germination, proteolytic removal of this internal inactivation region generates the active heterodimeric maize RIP with full N-glycosidase activity. This naturally occurring switch-on mechanism provides an opportunity for targeting the cytotoxin to pathogen-infected cells. Here, we report the addition of HIV-1 protease recognition sequences to the internal inactivation region and the activation of the maize RIP variants by HIV-1 protease in vitro and in HIV-infected cells. Among the variants generated, two were cleaved efficiently by HIV-1 protease. The HIV-1 protease-activated variants showed enhanced N-glycosidase activity in vivo as compared to their un-activated counterparts. They also possessed potent inhibitory effect on p24 antigen production in human T cells infected by two HIV-1 strains. This switch-on strategy for activating the enzymatic activity of maize RIP in target cells provides a platform for combating pathogens with a specific protease.
- Subjects :
- Anti-HIV Agents
medicine.medical_treatment
Recombinant Fusion Proteins
T-Lymphocytes
Molecular Sequence Data
Ribosome Inactivating Proteins
Biology
Ribosome
Zea mays
Cell Line
chemistry.chemical_compound
Antigen
HIV Protease
Genetics
medicine
Humans
Amino Acid Sequence
chemistry.chemical_classification
Protease
Ribosome-inactivating protein
Proteolytic enzymes
Enzyme Activation
Enzyme
Ricin
chemistry
Biochemistry
Cell culture
Synthetic Biology and Chemistry
HIV-1
tat Gene Products, Human Immunodeficiency Virus
Subjects
Details
- Language :
- English
- ISSN :
- 13624962 and 03051048
- Volume :
- 38
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....058b8d538daef7561733d94f8846ce46