Cell selectivity correlates with membrane-specific interactions: a case study on the antimicrobial peptide G15 derived from granulysin.
Cell selectivity correlates with membrane-specific interactions: a case study on the antimicrobial peptide G15 derived from granulysin.
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细胞选择性与膜特异性相互作用相关:来自颗粒溶素的抗菌肽 G15 的案例研究。
DOI:
10.1016/j.bbamem.2006.02.014
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发表时间:
2006
期刊:
影响因子:
--
通讯作者:
Krensky,AlanM
中科院分区:
文献类型:
--
作者:
Ramamoorthy,Ayyalusamy;Thennarasu,Sathiah;Tan,Anmin;Lee,Dong-Kuk;Clayberger,Carol;Krensky,AlanM
A 15-residue peptide dimer G15 derived from the cell lytic protein granulysin has been shown to exert potent activity against microbes, including E. coli, but not against human Jurkat cells [Z. Wang, E. Choice, A. Kaspar, D. Hanson, S. Okada, S.C. Lyu, A.M. Krensky, C. Clayberger, Bactericidal and tumoricidal activities of synthetic peptides derived from granulysin. J. Immunol. 165 (2000) 1486–1490]. We investigated the target membrane selectivity of G15 using fluorescence, circular dichroism and31P NMR methods. The ANS uptake assay shows that the extent of E. coli outer membrane disruption depends on G15 concentration.31P NMR spectra obtained from E. coli total lipid bilayers incorporated with G15 show disruption of lipid bilayers. Fluorescence binding studies on the interaction of G15 with synthetic liposomes formed of E. coli lipids suggest a tight binding of the peptide at the membrane interface. The peptide also binds to negatively charged POPC/POPG (3:1) lipid vesicles but fails to insert deep into the membrane interior. These results are supported by the peptide-induced changes in the measured isotropic chemical shift and T1 values of POPG in 3:1 POPC:POPG multilamellar vesicles while neither a non-lamellar phase nor a fragmentation of bilayers was observed from NMR studies. The circular dichroism studies reveal that the peptide exists as a random coil in solution but folds into a less ordered conformation upon binding to POPC/POPG (3:1) vesicles. However, G15 does not bind to lipid vesicles made of POPC/POPG/Chl (9:1:1) mixture, mimicking tumor cell membrane. These results explain the susceptibility of E. coli and the resistance of human Jurkat cells to G15, and may have implications in designing membrane-selective therapeutic agents.
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DOI:
10.1111/j.1432-1033.1993.tb17677.x
发表时间:
1993-03-01
期刊:
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子:
--
作者:
GARCERA, MJG;ELFERINK, MGL;KONINGS, WN
通讯作者:
KONINGS, WN
影响因子:
3.4
作者:
BenTal, N;Honig, B;McLaughlin, S
通讯作者:
McLaughlin, S
影响因子:
2
作者:
Santos, JS;Lee, DK;Ramamoorthy, A
通讯作者:
Ramamoorthy, A
DOI:
--
发表时间:
1994
期刊:
Biochimica et Biophysica Acta
影响因子:
--
作者:
J. Killian;M. Koorengevel;J. Bouwstra;G. Gooris;W. Dowhan;B. de Kruijff
通讯作者:
B. de Kruijff
影响因子:
11.4
作者:
Kervinen, J;Tobin, GJ;Zdanov, A
通讯作者:
Zdanov, A