Synthetic Glycoforms Reveal Carbohydrate-Dependent Bioactivity of Human Saposin D
Christopher G. F. Graf
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorChristian Schulz
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Marina Schmälzlein
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Christian Heinlein
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorManuel Mönnich
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorLukas Perkams
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Markus Püttner
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Irene Boos
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorMarkus Hessefort
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorJose Nelson Lombana Sanchez
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Michael Weyand
Department of Biochemistry, Universität Bayreuth, Germany
Search for more papers by this authorProf. Clemens Steegborn
Department of Biochemistry, Universität Bayreuth, Germany
Search for more papers by this authorDr. Bernadette Breiden
LIMES Institute, Universität Bonn, Germany
Search for more papers by this authorDr. Günter Schwarzmann
LIMES Institute, Universität Bonn, Germany
Search for more papers by this authorProf. Konrad Sandhoff
LIMES Institute, Universität Bonn, Germany
Search for more papers by this authorCorresponding Author
Prof. Carlo Unverzagt
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorChristopher G. F. Graf
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorChristian Schulz
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Marina Schmälzlein
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Christian Heinlein
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorManuel Mönnich
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorLukas Perkams
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Markus Püttner
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Irene Boos
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorMarkus Hessefort
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorJose Nelson Lombana Sanchez
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorDr. Michael Weyand
Department of Biochemistry, Universität Bayreuth, Germany
Search for more papers by this authorProf. Clemens Steegborn
Department of Biochemistry, Universität Bayreuth, Germany
Search for more papers by this authorDr. Bernadette Breiden
LIMES Institute, Universität Bonn, Germany
Search for more papers by this authorDr. Günter Schwarzmann
LIMES Institute, Universität Bonn, Germany
Search for more papers by this authorProf. Konrad Sandhoff
LIMES Institute, Universität Bonn, Germany
Search for more papers by this authorCorresponding Author
Prof. Carlo Unverzagt
Bioorg. Chemie, Gebäude NWI, Universität Bayreuth, 95440 Bayreuth, Germany
Search for more papers by this authorGraphical Abstract
Lipid wrap: The main glycoforms of the hydrophobic lysosomal glycoprotein saposin D (SapD) were synthesized by native chemical ligation. In functional assays the lipid-binding properties of three SapD glycoforms S1–S3 were found to be affected by the sugar moiety of SapD and showed a dependency on the size and the type of N-glycan.
Abstract
The main glycoforms of the hydrophobic lysosomal glycoprotein saposin D (SapD) were synthesized by native chemical ligation. An approach for the challenging solid-phase synthesis of the fragments was developed. Three SapD glycoforms were obtained following a general and robust refolding and purification protocol. A crystal structure of one glycoform confirmed its native structure and disulfide pattern. Functional assays revealed that the lipid-binding properties of three SapD glycoforms are highly affected by the single sugar moiety of SapD showing a dependency of the size and the type of N-glycan.
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