Vestergaard Mikkel, Christensen Mikkel, Hansen Sara K, Grønvall Dennis, Kjølbye Lisbeth R, Vosegaard Thomas, Schiøtt Birgit
Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark.
Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark and Sino-Danish Center for Education and Research, Zhongguancun College, 271 N 4th Ring Road, Haidian, 100080 Beijing, China.
Biointerphases. 2017 May 5;12(2):02D405. doi: 10.1116/1.4982642.
Many antimicrobial peptides function by forming pores in the plasma membrane of the target cells. Intriguingly, some of these peptides are very short, and thus, it is not known how they can span the membrane, or whether other mechanisms of cell disruption are dominant. Here, the conformation and orientation of the 14-residue peptaibol SPF-5506-A (SPF) are investigated in lipid environments by atomistic and coarse grained molecular dynamics (MD) simulations, circular dichroism, and nuclear magnetic resonance (NMR) experiments. The MD simulations show that SPF is inserted spontaneously in a transmembrane orientation in both 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers resulting in thinning of the bilayers near the peptides, which drives the peptide aggregation. Furthermore, the backbone conformation of the peptide in the bilayer bound state is different from that of the NMR model solved in small bicelles. These results demonstrate that mutual adaption between the peptides and the membrane is likely to be important for pore formation.
许多抗菌肽通过在靶细胞的质膜上形成孔来发挥作用。有趣的是，其中一些肽非常短，因此，尚不清楚它们如何跨越膜，或者细胞破坏的其他机制是否占主导地位。在这里，通过原子和粗粒度分子动力学（MD）模拟、圆二色性和核磁共振（NMR）实验，研究了14个残基的肽菌素SPF-5506-A（SPF）在脂质环境中的构象和取向。MD模拟表明，SPF在1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱和1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱双层膜中以跨膜方向自发插入，导致肽附近的双层膜变薄，从而驱动肽聚集。此外，肽在双层结合状态下的主链构象与在小双分子层中解析的NMR模型不同。这些结果表明，肽与膜之间的相互适应可能对孔的形成很重要。
