Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate chain that modulates its enzyme activity

Rana El Masri (1) , Amal Seffouh (1) , Caroline Roelants (2) , Ilham Seffouh (3) , Evelyne Gout (1) , Julien Pérard (4) , Fabien Dalonneau (1) , Kazuchika Nishitsuji (5) , Fredrik Noborn (6) , Mahnaz Nikpour (6) , Göran Larson (6) , Yoann Crétinon (1) , Mélanie Friedel-Arboleas (1) , Kenji Uchimura (7) , Régis Daniel (3) , Hugues Lortat-Jacob (1) , Odile Filhol (2) , Romain R. Vivès (1)

1 IBS - UMR 5075 - Institut de biologie structurale
2 IMAC - Invasion mechanisms in angiogenesis and cancer
3 LAMBE - UMR 8587 - Laboratoire Analyse, Modélisation et Matériaux pour la Biologie et l'Environnement
4 BEE - BioEnergie et Environnement
5 Department of Biochemistry, Wakayama Medical University
6 GU - Göteborgs Universitet = University of Gothenburg
7 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576

Sulfs represent a class of unconventional sulfatases which provide an original post-synthetic regulatory mechanism for heparan sulfate polysaccharides and are involved in multiple physiopathological processes, including cancer. However, Sulfs remain poorly characterized enzymes, with major discrepancies regarding their in vivo functions. Here we show that human SuIf-2 (HSulf-2) harbors a chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain, attached to the enzyme substrate-binding domain. We demonstrate that this GAG chain affects enzyme/substrate recognition and tunes HSulf-2 activity in vitro and in vivo. In addition, we show that mammalian hyaluronidase acts as a promoter of HSulf-2 activity by digesting its GAG chain. In conclusion, our results highlight HSulf-2 as a proteoglycan-related enzyme and its GAG chain as a critical non-catalytic modulator of the enzyme activity. These findings contribute to clarifying the conflicting data on the activities of the Sulfs.

Domaines: Biochimie, Biologie Moléculaire

Rana El Masri, Amal Seffouh, Caroline Roelants, Ilham Seffouh, Evelyne Gout, et al.. Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate chain that modulates its enzyme activity. Cell Reports, 2022, 38 (11), pp.110516. ⟨10.1016/j.celrep.2022.110516⟩. ⟨hal-03637587⟩