1. Antimicrobial activity and conformation of gaegurin-6 amide and its analogs
K H Lee, S Y Hong, J E Oh, B J Lee, B S Choi Peptides. 1998;19(10):1653-8. doi: 10.1016/s0196-9781(98)00119-3.
A function of the intra-disulfide bridge located at the C-terminal of Rana peptides has not been extensively studied. To investigate the function of the disulfide bridge related to the activity and the structure, we chose Gaegurin-6, isolated from Rana rugosa as a model peptide and synthesized linear analogs. The reduction of the disulfide bridge resulted in the complete loss of antimicrobial activity while replacements of cysteines by serines retained antimicrobial activity. Circular dichroism spectra from a titration of the peptides in sodium dodecyl sulfate indicated that the disulfide bridge of Gaegurin-6 might stabilize the induction of an alpha helical structure in lipid membranes and the alpha helical forming propensity of the peptides correlated with antimicrobial activity.
2. Action mechanism and structural requirements of the antimicrobial peptides, gaegurins
Hyung-Sik Won, Su-Jin Kang, Bong-Jin Lee Biochim Biophys Acta. 2009 Aug;1788(8):1620-9. doi: 10.1016/j.bbamem.2008.10.021. Epub 2008 Nov 7.
Gaegurins (GGNs) are a family of cationic, alpha-helical, antimicrobial peptides that were isolated from a Korean frog, Glandirana emeljanovi (formerly classified as Rana rugosa) and represent one of the structurally well-characterized groups. Among six gaegurins, gaegurin 4 (renamed herein esculentin-2EM), gaegurin 5 (brevinin-1EMa), and gaegurin 6 (brevinin-1EMb) have been investigated comprehensively in terms of structure-activity relationships. In this paper, we first suggest renaming of gaegurins according to a recently raised rule of systematic nomenclature. Then, the current understanding of gaegurins is reviewed by summarizing their structure-activity relationships. In particular competing arguments on gaegurins are synthetically inspected. Finally their action mechanism and structural requirements will be discussed.
3. Gaegurin-6 stimulates insulin secretion through calcium influx in pancreatic beta Rin5mf cells
Ji Hae Kim, Jung Ok Lee, Jin Hee Jung, Soo Kyung Lee, Ga Young You, Sun Hwa Park, Hyeon Soo Kim Regul Pept. 2010 Jan 8;159(1-3):123-8. doi: 10.1016/j.regpep.2009.07.014.
Gaegurin-6, an antimicrobial peptide that belongs to the alpha-helix family, was isolated from the skin of Rana rugosa. Gaegurin-6 contains a hydrophobic motif at the N-terminus and a helical region at the C-terminus. Although gaegurin-6 has been implicated in cell signaling, the precise role in insulin secretion is currently unknown. We have attempted to determine whether gaegurin-6 affects insulin secretion and tried to elucidate the relationship between the structural motifs and biological activity. In this study, we have shown that gaegurin-6 stimulates insulin secretion and also increases the intracellular calcium concentration in pancreatic beta Rin5mf cells. Moreover, a corollary study revealed that both the hydrophobicity of the N-terminus and the disulfide bridge of the C-terminus of gaegurin-6 are critical for its effects on insulin secretion. Membrane pore-forming ability is also observed in gaegurin-6, but not in the linear form or the N-terminus hydrophobic amino acid-deleted form. We further showed that these regions of gaegurin-6 are responsible for calcium influx in pancreatic beta Rin5mf cells. Taken together, these results indicate that gaegurin-6 can affect insulin secretion in pancreatic beta cells through the modulation of calcium influx.
