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

This study unveiled the HINT structure, including an adduct recognition region, explored interactions with heparin, and suggested a regulatory role in auto-processing. These findings enhance our understanding of HINT fold evolution and its potential biotechnological uses. 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 fromTetrahymena 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.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research