A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells
| Autor: | Pang-Chui Shaw, Yong-Tang Zheng, Amanda Nga-Sze Mak, Sue Ka-Yee Law, Kam-Bo Wong, Rui-Rui Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
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 |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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