Sood Rohit, Domanov Yegor, Kinnunen Paavo K J
Helsinki Biophysics and Biomembrane Group, Medical Biochemistry, Institute of Biomedicine, University of Helsinki, PO Box 63 (Haartmaninkatu 8), Helsinki, FIN-00014 Finland.
J Fluoresc. 2007 Mar;17(2):223-34. doi: 10.1007/s10895-007-0161-9. Epub 2007 Feb 6.
Temporins are short (10-13 amino acids) and linear antimicrobial peptides first isolated from the skin of the European red frog, Rana temporaria, and are effective against Gram-positive bacteria and Candida albicans. Similarly to other antimicrobial peptides, the association of temporins to lipid membranes has been concluded to underlie their antimicrobial effects. Accordingly, a detailed understanding of their interactions with phospholipids is needed. We conjugated a fluorophore (Texas Red) to a Cys containing derivative of temporin B (temB) and investigated its binding to liposomes by fluorescence spectroscopy. Circular dichroic spectra for the Cys-mutant recorded in the absence and in the presence of phospholipids were essentially similar to those for temB. A blue shift in the emission spectra and diminished quenching by ferrocyanide (FCN) of Texas Red labeled temporin B (TRC-temB) were seen in the presence of liposomes. Both of these changes can be attributed to the insertion of the Texas Red into the hydrophobic region of the bilayer. Resonance energy transfer, steady state anisotropy, and fluorescence lifetimes further demonstrate the interaction of TRC-temB with liposomes to be enhanced by negatively charged phospholipids. Instead, cholesterol attenuates the association of TRC-temB with membranes. The interactions between TRC-temB and liposomes of varying negative surface charge are driven by electrostatics as well as hydrophobicity. Similarly to native temporin B also TRC-temB forms amyloid type fibers in the presence of negatively charged liposomes. This property is likely to relate to the cytotoxic activity of this peptide.
temporins是一类短肽(10 - 13个氨基酸),呈线性,最初从欧洲赤蛙(林蛙)的皮肤中分离得到,对革兰氏阳性菌和白色念珠菌有效。与其他抗菌肽类似,temporins与脂质膜的结合被认为是其抗菌作用的基础。因此,需要详细了解它们与磷脂的相互作用。我们将一种荧光团(德克萨斯红)与含半胱氨酸的temporin B(temB)衍生物偶联,并通过荧光光谱研究其与脂质体的结合。在不存在和存在磷脂的情况下记录的半胱氨酸突变体的圆二色光谱与temB的光谱基本相似。在脂质体存在的情况下,观察到德克萨斯红标记的temporin B(TRC - temB)的发射光谱发生蓝移,并且亚铁氰化物(FCN)对其的猝灭作用减弱。这两种变化都可归因于德克萨斯红插入双层膜的疏水区域。共振能量转移、稳态各向异性和荧光寿命进一步证明,带负电荷的磷脂会增强TRC - temB与脂质体的相互作用。相反,胆固醇会减弱TRC - temB与膜的结合。TRC - temB与具有不同负表面电荷的脂质体之间的相互作用是由静电和疏水性驱动的。与天然temporin B类似,TRC - temB在带负电荷的脂质体存在下也会形成淀粉样纤维。这种特性可能与该肽的细胞毒性活性有关。