Amyloidogenic Protein Interactors

Nanobodies

Camels, dromedaries, llamas, alpacas (but also sharks) possess IgG’s formed by heavy chains only.

The variable domain of heavy-chain antibodies, VHH, is expressed to be used as nanobody. A specific nanobody, Nb24, prevents in vitro fibrillogenesis of D76N β2-m, a highly amyloidogenic protein, and alters its tissue distribution in vivo.

NMR Epitope Mapping: from the spectrum perturbation it is possible to localize the binding region.

NMR spectrum of D76N b2-m, free and bound to Nb24 nanobody

NMR spectrum of D76N β2-m, free and bound to Nb24 nanobody

Nanoparticles

Citrate-coated gold nanoparticles, Cit-AuNPs, display specific interaction with the amyloidogenic protein family of β2-m variants. NMR-based mappingand modeling show that a dimeric adduct is consistent with the interaction interface between protein and NPs..

Figue 01:NMR-based mapping - D76N b2-mD76N b2-m + Cit-AuNP

Figure02: NMR-based mapping - D76N b2-mD76N b2-m + Cit-AuNP

The interaction with Cit-AuNPs prevents fibrillogenesis

Trefoil Knot

Trefoil Knot, TK, is a supramolecular assembly of three interlaced units of an organic ligand, with three crossings and three coordinated Zn²⁺ ions. It was obtained and characterized by the group of prof. Trabolsi.

TK establishes a preferentially-oriented, fast-exchange interaction with D76N β2-m that preserves the protein structure and prevents fibrillogenesis

Figure 02 and 03 Amyloidogenic Protein Interactors