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Roles of histidine charge and cardiolipin in membrane disruption by antimicrobial peptides Gaduscidin-1 and Gaduscidin-2.
Biochimica et Biophysica Acta (BBA) - Biomembranes ( IF 2.8 ) Pub Date : 2020-08-19 , DOI: 10.1016/j.bbamem.2020.183444
Gagandeep Sandhu 1 , Michael R Morrow 1 , Valerie Booth 2
Affiliation  

Gad-1 and Gad-2 are helical, histidine-rich antimicrobial peptides (AMPs) from paralogous genes in cod. 15N and 2H solid state nuclear magnetic resonance (NMR) were used to characterize their lipid-bound structures and lipid interactions. Gad-1 was found to position in-plane in POPC: POPG bilayers. Gad-1 displayed greater effects than Gad-2 on lipid acyl chain order of POPE: POPG and POPE: POPG: CL bilayers, in keeping with its greater activity against E. coli. The effect of Gad-1 and Gad-2 on lipid bilayer order was only weakly affected by changes in pH, and hence changes in histidine charge. This was somewhat surprising for Gad-2 as this peptide's biological activity has been shown to be greater at low pH and thus the finding may point to the existence of functional interactions with non-lipid components of bacteria. The incorporation of cardiolipin into POPE: POPG bilayers in such a way as to preserve the overall charge of the bilayers did not alter Gad-1's effects on lipid acyl chain order parameters, which report on motions on the 10−5 s timescale. When cardiolipin and Gad-1 were both present, there were subtle changes on membrane dynamics at other timescales.



中文翻译:

组氨酸电荷和心磷脂在抗菌肽Gaduscidin-1和Gaduscidin-2破坏膜中的作用。

Gad-1和Gad-2是来自鳕鱼中旁系同源基因的螺旋,富含组氨酸的抗菌肽(AMP)。15 N和2 H固态核磁共振(NMR)用于表征它们的脂质结合结构和脂质相互作用。发现Gad-1位于POPC:POPG双层中的平面内。Gad-1对POPE:POPG和POPE:POPG:CL双层的脂酰基链显示出比Gad-2更大的作用,同时保持了对大肠杆菌的更大活性。Gad-1和Gad-2对脂质双层顺序的影响仅受到pH值变化的微弱影响,因此也影响组氨酸电荷的变化。对于Gad-2,这有些令人惊讶,因为该肽的生物活性在低pH下显示出更高的活性,因此该发现可能表明存在与细菌非脂质成分的功能性相互作用。以保持双层的总电荷的方式将心磷脂并入POPE:POPG双层中,不会改变Gad-1对脂质酰基链顺序参数的影响,后者报告了10 -5  s时标上的运动。当心磷脂和Gad-1均存在时,在其他时间尺度上膜动力学有细微的变化。

更新日期:2020-08-24
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