Institute for Molecular Bioscience, The University of Queensland , Brisbane, Queensland 4072, Australia.
J Am Chem Soc. 2016 May 4;138(17):5706-13. doi: 10.1021/jacs.6b02575. Epub 2016 Apr 26.
Enantiomeric forms of BTD-2, PG-1, and PM-1 were synthesized to delineate the structure and function of these β-sheet antimicrobial peptides. Activity and lipid-binding assays confirm that these peptides act via a receptor-independent mechanism involving membrane interaction. The racemic crystal structure of BTD-2 solved at 1.45 Å revealed a novel oligomeric form of β-sheet antimicrobial peptides within the unit cell: an antiparallel trimer, which we suggest might be related to its membrane-active form. The BTD-2 oligomer extends into a larger supramolecular state that spans the crystal lattice, featuring a steric-zipper motif that is common in structures of amyloid-forming peptides. The supramolecular structure of BTD-2 thus represents a new mode of fibril-like assembly not previously observed for antimicrobial peptides, providing structural evidence linking antimicrobial and amyloid peptides.
为了阐明这些β-折叠型抗菌肽的结构和功能，我们合成了 BTD-2、PG-1 和 PM-1 的对映异构体。活性和脂质结合实验证实，这些肽通过一种不依赖于受体的机制发挥作用，涉及膜相互作用。BTD-2 的外消旋晶体结构在 1.45Å 处得到解决，揭示了单位晶胞内β-折叠型抗菌肽的一种新型寡聚形式：反平行三聚体，我们推测这可能与其膜活性形式有关。BTD-2 寡聚体延伸成更大的超分子状态，跨越晶格，具有在淀粉样肽结构中常见的空间拉链模式。因此，BTD-2 的超分子结构代表了一种以前在抗菌肽中未观察到的新的类似纤维状组装模式，为连接抗菌肽和淀粉样肽提供了结构证据。
