Structure and functional impact of glycosaminoglycan modification of HSulf-2 endosulfatase revealed by atomic force microscopy and mass spectrometry - Archive ouverte HAL
Article Dans Une Revue Scientific Reports Année : 2023

Structure and functional impact of glycosaminoglycan modification of HSulf-2 endosulfatase revealed by atomic force microscopy and mass spectrometry

Résumé

AbstractThe human sulfatase HSulf-2 is one of only two known endosulfatases that play a decisive role in modulating the binding properties of heparan sulfate proteoglycans on the cell surface and in the extracellular matrix. Recently, HSulf-2 was shown to exhibit an unusual post-translational modification consisting of a sulfated glycosaminoglycan chain. This study describes the structural characterization of this glycosaminoglycan (GAG) and provides new data on its impact on the catalytic properties of HSulf-2. The unrevealed nature of this GAG chain is identified as a chondroitin/dermatan sulfate (CS/DS) mixed chain, as shown by mass spectrometry combined with NMR analysis. It consists primarily of 6-O and 4-O monosulfated disaccharide units, with a slight predominance of the 4-O-sulfation. Using atomic force microscopy, we show that this unique post-translational modification dramatically impacts the enzyme hydrodynamic volume. We identified human hyaluronidase-4 as a secreted hydrolase that can digest HSulf-2 GAG chain. We also showed that HSulf-2 is able to efficiently 6-O-desulfate antithrombin III binding pentasaccharide motif, and that this activity was enhanced upon removal of the GAG chain. Finally, we identified five N-glycosylation sites on the protein and showed that, although required, reduced N-glycosylation profiles were sufficient to sustain HSulf-2 integrity.

Domaines

Biochimie [q-bio.BM] Chimie analytique Biophysique Biologie structurale [q-bio.BM]
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https://hal.science/hal-04348199

Soumis le : samedi 16 décembre 2023-07:27:22

Dernière modification le : mercredi 18 décembre 2024-10:10:27

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Dates et versions

hal-04348199 , version 1 (16-12-2023)

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Ilham Seffouh, Mélanie Bilong, Cédric Przybylski, Nesrine El Omrani, Salomé Poyer, et al.. Structure and functional impact of glycosaminoglycan modification of HSulf-2 endosulfatase revealed by atomic force microscopy and mass spectrometry. Scientific Reports, 2023, 13 (1), ⟨10.1038/s41598-023-49147-5⟩. ⟨hal-04348199⟩

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