The three-dimensional structure of the Vint domain from Tetrahymena thermophila suggests a ligand-regulated cleavage mechanism by the HINT fold.

Hideo Iwaï, Hannes M Beyer, Julia E M Johansson, Mi Li, Alexander Wlodawer

FEBS letters 2024 Apr

filter terms:

Vint proteins have been identified in unicellular metazoans as a novel hedgehog-related gene family, merging the von Willebrand factor type A domain and the Hedgehog/INTein (HINT) domains. We present the first three-dimensional structure of the Vint domain from Tetrahymena thermophila corresponding to the auto-processing domain of hedgehog proteins, shedding light on the unique features, including an adduct recognition region (ARR). Our results suggest a potential binding between the ARR and sulfated glycosaminoglycans like heparin sulfate. Moreover, we uncover a possible regulatory role of the ARR in the auto-processing by Vint domains, expanding our understanding of the HINT domain evolution and their use in biotechnological applications. Vint domains might have played a crucial role in the transition from unicellular to multicellular organisms. © 2024 Federation of European Biochemical Societies.

Citation

Hideo Iwaï, Hannes M Beyer, Julia E M Johansson, Mi Li, Alexander Wlodawer. The three-dimensional structure of the Vint domain from Tetrahymena thermophila suggests a ligand-regulated cleavage mechanism by the HINT fold. FEBS letters. 2024 Apr;598(8):864-874