Fig. 5: Structural Model of inhibition of IAPP fibril formation by PFD.
From: Structural basis for the inhibition of IAPP fibril formation by the co-chaperonin prefoldin
Schematic model describing the inhibition mechanism of PFD on IAPP fibril formation. PFD interacts with monomeric IAPP, but this transient interaction does not lead to a significant decrease of the lag-phase. a, b present docking models of the complex between monomeric IAPP (PDB: 2L86) and PhPFD (PDB: 2ZDI) based on NMR derived interaction information (Figs. 2 and 3). c Inhibition of secondary nucleation and elongation results from coverage of fibril surface and ends by PFD (Fig. 4). The presence of PFD leads to a decreased steady phase fibril mass (Fig. 1a), which results from the formation of less aggregates with an altered morphology (Fig. 1b). The inset zoom represents a model of IAPP fibril structure with unfolded residues 1–12 in yellow and the structured fibril core is represented in purple (from residues 13–37). d, e present docking models of PhPFD (PDB: 2ZDI) on IAPP fibril (PDB: 6Y1A) surface and extremities, respectively, integrating structural information obtained by NMR (Figs. 2 and 3) and EM (Fig. 4); the black arrows indicate the fibril axis with the tips pointing towards the fibril ends.
