Figure 1 | Scientific Reports

Figure 1

From: Substoichiometric inhibition of transthyretin misfolding by immune-targeting sparsely populated misfolding intermediates: a potential diagnostic and therapeutic for TTR amyloidoses

Figure 1

(A) Proposed model for the inhibition of TTR fibrillogenesis by the misTTR antibody. During the fibril formation process, native tetrameric TTR first dissociates into an altered monomeric intermediate. This altered monomeric intermediate self assembles into stable nuclei, which allows for fibril formation to proceed. Substoichiometric amounts of the misTTR antibody may suppress TTR fibril formation by binding misfolded conformations of the TTR that comprise the critical nuclei, which are likely present at very low concentrations. The misTTR antibody may also act to inhibit TTR fibrillogenesis by binding to the unfolded monomers and/or to the extremities of fibrils, essentially capping the ends of preformed fibrils to prevent fibril growth. (B) Surface representation of native tetrameric TTR (green) with buried misTTR epitope in red. (C) Surface representation of monomeric TTR (green) with exposed epitope in red. Structures were generated using PDB ID 1DVQ in Deep View (Swiss-PBD Viewer 3.7).

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