Affiliation:
1. Institute of Biotechnology University of Helsinki Finland
2. Center for Structural Biology National Cancer Institute Frederick MD USA
3. Basic Science Program Frederick National Laboratory for Cancer Research MD USA
Abstract
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.