Unraveling the conformational landscape of amyloid precursor protein intracellular domain.

ABSTRACT: The amyloid precursor protein intracellular domain (AICD), a cleavage product of amyloid precursor protein implicated in Alzheimer disease and amyloid lateral sclerosis, is a functionally important but structurally elusive intrinsically disordered protein. In this study, we investigate the conformational ensemble of a 35-residue AICD segment encompassing the conserved YENPTY motif using molecular dynamics simulations, small-angle x-ray scattering, circular dichroism, and nuclear magnetic resonance data. Our results reveal that AICD fluctuates between compact and extended states, exhibiting dynamic secondary structure elements and heterogeneous solvent accessibility. Small-angle x-ray scattering and circular dichroism analyses support a partially compact, flexible ensemble, whereas time-lag

SUBMITTER: Mandal N 

PROVIDER: S-EPMC12709260 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature