Helix-Aggregation Interplay in Nucleophosmin 1: Structural, Morphological, and Cytotoxic Consequences of Fragment Length

showing the strongest effect; however, helix-stabilizing conditions reduced cytotoxicity. Together, these findings demonstrate that N-terminal extension exerts a protective effect on the aggregation-prone 264-277 region by stabilizing local α-helical structure and delaying the α → β transition that underlies NPM1 aggregation, thereby attenuating fibril formation and cytotoxicity. These results suggest that helical stabilization could limit the aggregation propensity of C-terminal regions of NPM1 and exert a potential protective mechanism against its misfolding.