The Flexible and Clustered Lysine Residues of Human Ribonuclease 7 Are Critical for Membrane Permeability and Antimicrobial Activity

Huang, Yu-Chie; Lin, Yu-Min; Chang, Ting-Wei; Wu, Shih-Jung; Lee, Yan-Shin; Chang, Margaret Dah‐Tsyr; Chen, Chinpan; Wu, Shih‐Hsiung; Liao, You‐Di

doi:10.1074/jbc.m607321200

Cited by 103 publications

(124 citation statements)

References 28 publications

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“…However, the most relevant result is the finding that their bactericidal activity is preserved not only after inactivation of their ribonucleolytic activity, but also after denaturation of the proteins. Clearly, the finding that bactericidal RNases do not use their ribonucleolytic activity for killing bacteria is not new, as it has been reported also for other bactericidal RNases [31][32][33]. Certainly surprising is instead the finding that they can perform a biological function, such as host-defence, a mechanism of innate immunity, while devoid of any structure.…”

Section: Discussionmentioning

confidence: 99%

“…In ZF-RNase-5 this helix, which encompasses residues [24][25][26][27][28][29][30][31][32][33][34][35], has a first turn in a 3 10 conformation, and terminates with a turn in a π helix conformation with main chain hydrogen bonds Met31-Ile36 and Ser32-Lys35 and Lys35 in the Lα conformation. In the corresponding region (residues 23-36) of ZF-RNase-1 [4] the network of hydrogen bonds (Ile30-Ile37 and Gly31-Lys36) is spatially conserved.…”

Section: Introductionmentioning

confidence: 99%

“…Thus the topology of this fragment is substantially unchanged with respect to ZF-RNase-5, although the insertion of the two residues formally breaks the helix at the level of Ile30 (Figure 2 and supplemental Figure S3). In the case of ZF-RNase-3 (residues [23][24][25][26][27][28][29][30][31][32][33][34][35] [4] the first turn of the helix is highly distorted.…”

Section: Introductionmentioning

confidence: 99%

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A new RNase sheds light on the RNase/angiogenin subfamily from zebrafish

Pizzo

Merlino

Turano

et al. 2010

Biochemical Journal

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Recently, extracellular RNases of the RNase A superfamily, with the characteristic CKxxNTF sequence signature, have been identified in fish. This has led to the recognition that these RNases are present in the whole vertebrate subphylum. In fact, they comprise the only enzyme family unique to vertebrates. Four RNases from zebrafish (Danio rerio) have been previously reported and have a very low RNase activity; some of these are endowed, like human angiogenin, with powerful angiogenic and bactericidal activities. In the present paper, we report the three-dimensional structure, the thermodynamic behaviour and the biological properties of a novel zebrafish RNase, ZF-RNase-5. The investigation of its structural and functional properties, extended to all other subfamily members, provides an inclusive description of the whole zebrafish RNase subfamily

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A new RNase sheds light on the RNase/angiogenin subfamily from zebrafish

Pizzo

Merlino

Turano

et al. 2010

Biochemical Journal

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“…The flexible structure of a protein is favorable for permeation across the cell membrane. For example, both human ribonuclease 7 and piscidin 1 (a novel cytotoxic peptide) analog with flexible structure are found with a marked increase in membrane permeability to incorporate into the bacterial membrane for a high antibacterial activity (Huang et al, 2007;Kim et al, 2010a). Therefore, we suggested that a flexible INS is favorable for permeating through the intestine epithelial cell membrane.…”

Section: Discussionmentioning

confidence: 94%

A natural lipopeptide of surfactin for oral delivery of insulin

et al. 2016

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Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid a-helix and b-turn, but with increased flexible b-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.

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“…The main source of RNKase 7 is keratinocytes. The peptide has molecular mass of 14,5 kDa, and destroys cytoplasmic membrane of different microorganisms even at low temperature (4 °С) and during some minutes (Huang et al, 2007). The lethal dose of RNKase 7 against vancomicin-resistant Enterococcus faecium was 30 nM.…”

Section: Antimicrobial Peptides In Local Defence Of Skinmentioning

confidence: 99%