| Structural highlights
Function
[RNAS7_HUMAN] Exhibits a potent RNase activity. Has broad-spectrum antimicrobial activity against many pathogenic microorganisms and remarkably potent activity (lethal dose of 90% < 30 nM) against a vancomycin resistant Enterococcus faecium.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The ubiquitous ribonucleases (RNases) play important roles in RNA metabolism, angiogenesis, neurotoxicity, and antitumor or antimicrobial activity. Only the antimicrobial RNases possess high positively charged residues, although their mechanisms of action remain unclear. Here, we report on the role of cationic residues of human RNase7 (hRNase7) in its antimicrobial activity. It exerted antimicrobial activity against bacteria and yeast, even at 4 degrees C. The bacterial membrane became permeable to the DNA-binding dye SYTOX(R) Green in only a few minutes after bactericidal RNase treatment. NMR studies showed that the 22 positively charged residues (Lys(18) and Arg(4)) are distributed into three clusters on the surface of hRNase7. The first cluster, K(1),K(3),K(111),K(112), was located at the flexible coil near the N terminus, whereas the other two, K(32),K(35) and K(96),R(97),K(100), were located on rigid secondary structures. Mutagenesis studies showed that the flexible cluster K(1),K(3),K(111),K(112), rather than the catalytic residues His(15), Lys(38), and His(123) or other clusters such as K(32),K(35) and K(96),R(97),K(100), is critical for the bactericidal activity. We suggest that the hRNase7 binds to bacterial membrane and renders the membrane permeable through the flexible and clustered Lys residues K(1),K(3),K(111),K(112). The conformation of hRNase7 can be adapted for pore formation or disruption of bacterial membrane even at 4 degrees C.
The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity.,Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD J Biol Chem. 2007 Feb 16;282(7):4626-33. Epub 2006 Dec 6. PMID:17150966[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Harder J, Schroder JM. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J Biol Chem. 2002 Nov 29;277(48):46779-84. Epub 2002 Sep 18. PMID:12244054 doi:http://dx.doi.org/10.1074/jbc.M207587200
- ↑ Zhang J, Dyer KD, Rosenberg HF. Human RNase 7: a new cationic ribonuclease of the RNase A superfamily. Nucleic Acids Res. 2003 Jan 15;31(2):602-7. PMID:12527768
- ↑ Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD. The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity. J Biol Chem. 2007 Feb 16;282(7):4626-33. Epub 2006 Dec 6. PMID:17150966 doi:10.1074/jbc.M607321200
- ↑ Huang YC, Lin YM, Chang TW, Wu SJ, Lee YS, Chang MD, Chen C, Wu SH, Liao YD. The flexible and clustered lysine residues of human ribonuclease 7 are critical for membrane permeability and antimicrobial activity. J Biol Chem. 2007 Feb 16;282(7):4626-33. Epub 2006 Dec 6. PMID:17150966 doi:10.1074/jbc.M607321200
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