Department Chemistry and Biochemistry, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
Angew Chem Int Ed Engl. 2017 Aug 7;56(33):9816-9819. doi: 10.1002/anie.201704618. Epub 2017 Jul 28.
Amyloid-β peptide (Aβ) isoforms of different lengths and aggregation propensities coexist in vivo. These different isoforms are able to nucleate or frustrate the assembly of each other. N-terminally truncated Aβ and Aβ make up one fifth of plaque load yet nothing is known about their interaction with full-length Aβ . We show that in contrast to C-terminally truncated isoforms, which do not co-fibrillize, deletions of ten residues from the N terminus of Aβ have little impact on its ability to co-fibrillize with the full-length counterpart. As a consequence, N-terminally truncated Aβ will accelerate fiber formation and co-assemble into short rod-shaped fibers with its full-length Aβ counterpart. This has implications for the assembly kinetics, morphology, and toxicity of all Aβ isoforms.
淀粉样β肽（Aβ）的不同长度和聚集倾向的异构体在体内共存。这些不同的异构体能够引发或阻碍彼此的组装。N 端截断的 Aβ和 Aβ占斑块负荷的五分之一，但人们对它们与全长 Aβ的相互作用一无所知。我们表明，与不共纤的 C 端截断异构体相反，从 Aβ的 N 端缺失十个残基对其与全长对应物共纤的能力几乎没有影响。因此，N 端截断的 Aβ将加速纤维形成，并与全长 Aβ共同组装成短棒状纤维。这对所有 Aβ异构体的组装动力学、形态和毒性都有影响。
