C-Mannosylation Enhances the Structural Stability of Human RNase 2
Summary: C-Mannosylation is a relatively rare form of protein glycosylation involving the attachment of an α-mannopyranosyl residue to C-2 of the indole moiety of the amino acid tryptophan. This type of linkage was initially discovered in RNase 2 from human urine but later confirmed to be present in...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220305599 |
| _version_ | 1818328601203834880 |
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| author | Martin Frank Daniela Beccati Bas R. Leeflang Johannes F.G. Vliegenthart |
| author_facet | Martin Frank Daniela Beccati Bas R. Leeflang Johannes F.G. Vliegenthart |
| author_sort | Martin Frank |
| collection | DOAJ |
| description | Summary: C-Mannosylation is a relatively rare form of protein glycosylation involving the attachment of an α-mannopyranosyl residue to C-2 of the indole moiety of the amino acid tryptophan. This type of linkage was initially discovered in RNase 2 from human urine but later confirmed to be present in many other important proteins. Based on NMR experiments and extensive molecular dynamics simulations on the hundred microsecond timescale we demonstrate that, for isolated glycopeptides and denatured RNase 2, the C-linked mannopyranosyl residue exists as an ensemble of conformations, among which 1C4 is the most abundant. However, for native RNase 2, molecular dynamics and NMR studies revealed that the mannopyranosyl residue favors a specific conformation, which optimally stabilizes the protein fold through a network of hydrogen bonds and which leads to a significant reduction of the protein dynamics on the microsecond timescale. Our findings contribute to the understanding of the biological role of C-mannosylation. |
| first_indexed | 2024-12-13T12:34:45Z |
| format | Article |
| id | doaj.art-d9b622e471fd43a3aa43401b1f844ead |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-13T12:34:45Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d9b622e471fd43a3aa43401b1f844ead2022-12-21T23:45:54ZengElsevieriScience2589-00422020-08-01238101371C-Mannosylation Enhances the Structural Stability of Human RNase 2Martin Frank0Daniela Beccati1Bas R. Leeflang2Johannes F.G. Vliegenthart3Biognos AB, Box 8963, Göteborg 40274, SwedenBijvoet Center, Division of Bio-Organic Chemistry, Utrecht University, Padualaan 8, Utrecht 3584 CH, The NetherlandsBijvoet Center, Division of Bio-Organic Chemistry, Utrecht University, Padualaan 8, Utrecht 3584 CH, The NetherlandsBijvoet Center, Division of Bio-Organic Chemistry, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands; Corresponding authorSummary: C-Mannosylation is a relatively rare form of protein glycosylation involving the attachment of an α-mannopyranosyl residue to C-2 of the indole moiety of the amino acid tryptophan. This type of linkage was initially discovered in RNase 2 from human urine but later confirmed to be present in many other important proteins. Based on NMR experiments and extensive molecular dynamics simulations on the hundred microsecond timescale we demonstrate that, for isolated glycopeptides and denatured RNase 2, the C-linked mannopyranosyl residue exists as an ensemble of conformations, among which 1C4 is the most abundant. However, for native RNase 2, molecular dynamics and NMR studies revealed that the mannopyranosyl residue favors a specific conformation, which optimally stabilizes the protein fold through a network of hydrogen bonds and which leads to a significant reduction of the protein dynamics on the microsecond timescale. Our findings contribute to the understanding of the biological role of C-mannosylation.http://www.sciencedirect.com/science/article/pii/S2589004220305599BiochemistryStructural BiologyProtein Structure Aspects |
| spellingShingle | Martin Frank Daniela Beccati Bas R. Leeflang Johannes F.G. Vliegenthart C-Mannosylation Enhances the Structural Stability of Human RNase 2 iScience Biochemistry Structural Biology Protein Structure Aspects |
| title | C-Mannosylation Enhances the Structural Stability of Human RNase 2 |
| title_full | C-Mannosylation Enhances the Structural Stability of Human RNase 2 |
| title_fullStr | C-Mannosylation Enhances the Structural Stability of Human RNase 2 |
| title_full_unstemmed | C-Mannosylation Enhances the Structural Stability of Human RNase 2 |
| title_short | C-Mannosylation Enhances the Structural Stability of Human RNase 2 |
| title_sort | c mannosylation enhances the structural stability of human rnase 2 |
| topic | Biochemistry Structural Biology Protein Structure Aspects |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220305599 |
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