Role of unique basic residues in cytotoxic, antibacterial and antiparasitic activities of human eosinophil cationic protein.
Summary of "Role of unique basic residues in cytotoxic, antibacterial and antiparasitic activities of human eosinophil cationic protein."
Abstract Eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin are members of the RNase A superfamily, which play a crucial role in host defense against various pathogens as they are endowed with several biological activities. Some of the biological activities possessed by ECP have been attributed to its strong basic character. In the current study, we have investigated the role of five unique basic residues, Arg22, Arg34, Arg61, Arg77 and His64 of ECP in its catalytic, cytotoxic, antibacterial and antiparasitic activities. These residues were changed to alanine to generate single and double mutants. None of the selected residues was found to be involved in the RNase activity of ECP. The substitution of all five residues individually was detrimental for the cytotoxic, antibacterial and antiparasitic activities of ECP; however, mutation of Arg22 and Arg34 resulted in the most significant effects. The double mutants also had reduced biological activities. All ECP mutants that had significantly reduced toxicity also had reduced membrane destabilization activity. Our study demonstrates that Arg22, Arg34, Arg61, Arg77 and His64 of ECP are crucial for its membrane destabilization activity, which appears to be the underlying mechanism of its cytotoxic, antibacterial and antiparasitic activities.
Affiliation
Immunochemistry Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Journal Details
This article was published in the following journal.
Name: Biological chemistry
ISSN: 1437-4315
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21303303
- DOI: http://dx.doi.org/10.1515/BC.2011.037
Medical and Biotech [MESH] Definitions
Eosinophil Major Basic Protein
One of several basic proteins released from EOSINOPHIL cytoplasmic granules. Eosinophil major basic protein is a 14-kDa cytotoxic peptide with a pI of 10.9. In addition to its direct cytotoxic effects, it stimulates the release of variety of INFLAMMATION MEDIATORS.
Muramidase
A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.
Interleukin-18
A cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK CELLS and CYTOTOXIC T-LYMPHOCYTES, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity.
Activities Of Daily Living
The performance of the basic activities of self care, such as dressing, ambulation, or eating.
Basic-leucine Zipper Transcription Factors
A large superfamily of transcription factors that contain a region rich in BASIC AMINO ACID residues followed by a LEUCINE ZIPPER domain.
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