Figure 5. Mutational landscape of the amyloid beta (Aß) amyloid fibril.

Average effect of mutations visualized on the cross-section of an Aß amyloid fibril (PDB accession 5KK3; Colvin et al., 2016). Nucleation gatekeeper residues and known familial Alzheimer’s disease (fAD) mutations positions are indicated by the wild-type (WT) aa identity on one of the two monomers; gatekeepers are indicated with blue dots and fAD are underlined. A single layer of the fibril is shown and the unstructured N-termini (aa 1-14) are shown with different random coil conformations for the two Aß monomers. See Figure 5—figure supplement 2 for alternative Aß42 amyloid polymorphs.

Figure 5—figure supplement 1. Modular organization of Aß42 and Aß40 polymorphs.

Linear organization of the Aß42 and Aß40 fibrils. Disordered/unstructured and structured residues are indicated.

Figure 5—figure supplement 2. Modular organization of mutational effects and gatekeepers visualized on Aß42 polymorphs.

Average effect of mutations visualized on the cross-section of various amyloid beta (Aß) amyloid polymorphs: PDB accession 2BEG (Lührs et al., 2005), 2MXU (Xiao et al., 2015), 5AEF (Schmidt et al., 2015), 2NAO (Wälti et al., 2016), and 5OQV (Gremer et al., 2017). Nucleation gatekeeper residues and known familial Alzheimer’s disease (fAD) mutations positions are indicated by the wild-type (WT) aa identity on one of the two monomers; gatekeepers are indicated with blue dots and fAD are underlined. A single layer of the fibril is shown and the unstructured N-termini are shown with different random coil conformations for the two Aß monomers.