Conformational plasticity of glycogenin and its maltosaccharide substrate during glycogen biogenesis
| العنوان: | Conformational plasticity of glycogenin and its maltosaccharide substrate during glycogen biogenesis |
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| المؤلفون: | F. von Delft, Udo Oppermann, Apirat Chaikuad, G. Berridge, D.S. Froese, Wyatt W. Yue |
| المصدر: | Proceedings of the National Academy of Sciences. 108:21028-21033 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Models, Molecular, Steric effects, Crystallography, Multidisciplinary, Glycogenin, Glycogen, biology, Protein Conformation, Stereochemistry, Mutation, Missense, Active site, Biological Sciences, chemistry.chemical_compound, Protein structure, X-Ray Diffraction, chemistry, Glucosyltransferases, biology.protein, Humans, Transferase, Glycogen synthase, Biogenesis, Glycoproteins |
| الوصف: | Glycogenin initiates the synthesis of a maltosaccharide chain covalently attached to itself on Tyr195 via a stepwise glucosylation reaction, priming glycogen synthesis. We have captured crystallographic snapshots of human glycogenin during its reaction cycle, revealing a dynamic conformational switch between ground and active states mediated by the sugar donor UDP-glucose. This switch includes the ordering of a polypeptide stretch containing Tyr195, and major movement of an approximately 30-residue “lid” segment covering the active site. The rearranged lid guides the nascent maltosaccharide chain into the active site in either an intra- or intersubunit mode dependent upon chain length and steric factors and positions the donor and acceptor sugar groups for catalysis. The Thr83Met mutation, which causes glycogen storage disease XV, is conformationally locked in the ground state and catalytically inactive. Our data highlight the conformational plasticity of glycogenin and coexistence of two modes of glucosylation as integral to its catalytic mechanism. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c3422eb7c39211bfadb626110389bb2cTest https://doi.org/10.1073/pnas.1113921108Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c3422eb7c39211bfadb626110389bb2c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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