Do Thanh D, LaPointe Nichole E, Sangwan Smriti, Teplow David B, Feinstein Stuart C, Sawaya Michael R, Eisenberg David S, Bowers Michael T
Department of Chemistry and Biochemistry and ‡Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California , Santa Barbara, California 93106, United States.
J Phys Chem B. 2014 Jul 3;118(26):7247-56. doi: 10.1021/jp502473s. Epub 2014 Jun 18.
Five different mutants of [Leu-5] Enkephalin YGGFL peptide have been investigated for fibril formation propensities. The early oligomer structures have been probed with a combination of ion-mobility mass spectrometry and computational modeling. The two peptides YVIFL and YVVFL form oligomers and amyloid-like fibrils. YVVFV shows an early stage oligomer distribution similar to those of the previous two, but amyloid-like aggregates are less abundant. Atomic resolution X-ray structures of YVVFV show two different modes of interactions at the dry interface between steric zippers and pairs of antiparallel β-sheets, but both are less favorable than the packing motif found in YVVFL. Both YVVFV and YVVFL can form a Class 6 steric zipper. However, in YVVFV, the strands between mating sheets are parallel to each other and in YVVFL they are antiparallel. The overall data highlight the importance of structurally characterizing high order oligomers within oligomerization pathways in studies of nanostructure assembly.
已对[亮氨酸-5]脑啡肽YGGFL肽的五种不同突变体的原纤维形成倾向进行了研究。已结合离子淌度质谱和计算建模对早期寡聚体结构进行了探测。两种肽YVIFL和YVVFL形成寡聚体和淀粉样原纤维。YVVFV显示出与前两者相似的早期寡聚体分布，但淀粉样聚集体较少。YVVFV的原子分辨率X射线结构显示，在空间拉链和反平行β-折叠对之间的干燥界面处存在两种不同的相互作用模式，但两者都不如YVVFL中发现的堆积基序有利。YVVFV和YVVFL都可以形成6类空间拉链。然而，在YVVFV中，配对片层之间的链彼此平行，而在YVVFL中它们是反平行的。总体数据突出了在纳米结构组装研究中，对寡聚化途径中的高阶寡聚体进行结构表征的重要性。
