Fig. 4

The possible role of CCs in the assembly pathway of ApCPEB PLD. Monomeric ApCPEB PLD fluctuates among β-, α-, and random coil conformations. In contrast to monomeric Orb2 PLD (bottom row), which remains as a mainly random coil in solution [16]. The association of α-helices present in monomeric ApCPEB PLD leads to the formation of CC species. CCs may mediate the conformational transition of neighboring random coil segments into β-sheet multimers [22, 47]. Alternatively, CCs may represent intermediate assembly structures facilitating their own conversion into β-sheet multimers. ApCPEB PLD and Orb2 PLD pathways converge in the formation of A11-reactive multimers, which can be trapped by AmB. A11-reactive multimers evolve to a common OC-reactive amyloid-like fold, which can be trapped by EGCG. QBP1, known to interact with poly-Q segments, blocks the monomer transition to a β-rich conformer which results in a reduction of M events in AFM-SMFS. In addition, QBP1 would potentially block the CCs transition to β-sheet multimers and hence, the amyloid-like assembly