Segmental isotope-labeling of the intrinsically disordered protein PQBP1

•We performed selective isotope-labeling of a C-terminal segment within PQBP1.•This is the first study to investigate disordered proteins by segmental labeling.•We demonstrated a very weak interaction between segments of disordered proteins.•Segmental labeling is useful for detecting weak intra-molecular interactions. Polyglutamine tract-binding protein 1 (PQBP1) is an intrinsically disordered protein abundantly expressed in the brain. Mutations in the PQBP1 gene are causative for X-linked mental retardation disorders. Here, we investigated the structure of the C-terminal segment within the context of full-length PQBP1. We produced a segmentally isotope-labeled PQBP1 composed of a non-labeled segment (residues 1–219; N-segment) and a 13C/15N-labeled segment (residues 220–265; C-segment). Our results demonstrate that the segmental isotope-labeling combined with NMR spectroscopy is useful for detecting a very weak intra-molecular interaction in an intrinsically disordered protein.