Ermakova Elena A, Kurbanov Rauf Kh
Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Lobachevsky Str., 2/31, 420111 Kazan, Russia.
Membranes (Basel). 2023 Mar 23;13(4):370. doi: 10.3390/membranes13040370.
The interaction of antimicrobial and amyloid peptides with cell membranes is a critical step in their activities. Peptides of the uperin family obtained from the skin secretion of Australian amphibians demonstrate antimicrobial and amyloidogenic properties. All-atomic molecular dynamics and an umbrella sampling approach were used to study the interaction of uperins with model bacterial membrane. Two stable configurations of peptides were found. In the bound state, the peptides in helical form were located right under the head group region in parallel orientation with respect to the bilayer surface. Stable transmembrane configuration was observed for wild-type uperin and its alanine mutant in both alpha-helical and extended unstructured forms. The potential of mean force characterized the process of peptide binding from water to the lipid bilayer and its insertion into the membrane, and revealed that the transition of uperins from the bound state to the transmembrane position was accompanied by the rotation of peptides and passes through the energy barrier of 4-5 kcal/mol. Uperins have a weak effect on membrane properties.
抗菌肽和淀粉样肽与细胞膜的相互作用是其发挥活性的关键步骤。从澳大利亚两栖动物皮肤分泌物中获得的uperin家族肽具有抗菌和淀粉样生成特性。采用全原子分子动力学和伞形采样方法研究uperin与模型细菌膜的相互作用。发现了肽的两种稳定构型。在结合状态下，螺旋形式的肽位于头部基团区域正下方，相对于双层表面呈平行取向。野生型uperin及其丙氨酸突变体在α-螺旋和伸展的无结构形式下均观察到稳定的跨膜构型。平均力势表征了肽从水到脂质双层的结合过程及其插入膜中的过程，并揭示了uperin从结合状态到跨膜位置的转变伴随着肽的旋转，且通过4-5千卡/摩尔的能垒。uperin对膜性质的影响较弱。
