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

التفاصيل البيبلوغرافية
العنوان: Structure and functional impact of glycosaminoglycan modification of HSulf-2 endosulfatase revealed by atomic force microscopy and mass spectrometry
المؤلفون: Seffouh, Ilham, Bilong, Mélanie, Przybylski, Cédric, El Omrani, Nesrine, Poyer, Salomé, Lamour, Guillaume, Clément, Marie-Jeanne, Boustany, Rebecca-Joe, Gout, Evelyne, Gonnet, Florence, Vivès, Romain, R, Daniel, Régis
المساهمون: Université Paris-Saclay, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Centre National de la Recherche Scientifique (CNRS), Laboratoire Analyse, Modélisation et Matériaux pour la Biologie et l'Environnement (LAMBE - UMR 8587), Université d'Évry-Val-d'Essonne (UEVE)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY)
المصدر: ISSN: 2045-2322.
بيانات النشر: HAL CCSD
Nature Publishing Group
سنة النشر: 2023
المجموعة: Université Paris Seine: ComUE (HAL)
مصطلحات موضوعية: [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
الوصف: International audience ; 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: hal-04348199; https://hal.science/hal-04348199Test; https://hal.science/hal-04348199/documentTest; https://hal.science/hal-04348199/file/Seffouh_et_al-2023-Scientific_Reports.pdfTest
DOI: 10.1038/s41598-023-49147-5
الإتاحة: https://doi.org/10.1038/s41598-023-49147-5Test
https://hal.science/hal-04348199Test
https://hal.science/hal-04348199/documentTest
https://hal.science/hal-04348199/file/Seffouh_et_al-2023-Scientific_Reports.pdfTest
حقوق: info:eu-repo/semantics/OpenAccess
رقم الانضمام: edsbas.14AC4697
قاعدة البيانات: BASE
الوصف
DOI:10.1038/s41598-023-49147-5