Residual structure in the Alzheimer's disease peptide: probing the origin of a central hydrophobic cluster

摘要: Background: Structure–function studies on the Alzheimer's disease peptide show that a central hydrophobic cluster – A β (17–21), LVFFA is prominent structural feature linked to plaque competence. The origin and stability of this was probed in 17-residue fragment which includes flanking residues potentially help stabilize cluster. Results: After residue substitution, measurement pK s, amide exchange rates other NMR data any coulombic interactions between His14 Glu22 are not required for In contrast, single substitution within disrupts its integrity causes largest shift residues, while increasing solvent accessibility backbone. Conclusions: structurally dominant relies primarily upon local interactions, rather than sidechains charged residues. Moreover, conformational disposition affects s underscoring dominance.