Holland, Lou, Pham, Phuong Thao, Bagdonas, Haroldas et al. (3 more authors) (2025) Methods for detecting, building, and improving tryptophan mannosylation in glycoprotein structures. Protein science : a publication of the Protein Society. e70025. ISSN 1469-896X
Abstract
Tryptophan mannosylation, the covalent addition of an α-ᴅ-mannose sugar to a tryptophan side chain, is a post-translational modification (PTM) that can affect protein stability, folding, and interactions. Compared to other forms of protein glycosylation, it is relatively uncommon but is affected by conformational anomalies and modeling errors similar to those seen in N- and O-glycans in the Protein Data Bank (PDB). In this work, we report methods for detecting, building, and improving mannose structures linked to tryptophans. These methods have been used to mine X-ray crystallographic and cryo-electron microscopy maps in the PDB looking for unmodeled mannosylation, resulting in a number of cases where the modification can be placed in the map with high confidence. Additionally, we address most conformational issues affecting this modification. Finally, the development of a structural template to recognize thrombospondin repeats (TSR) domains where tryptophan mannosylation occurs will allow for the mannosylation of candidate-predicted models, for example, those predicted with AlphaFold.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. |
Keywords: | Tryptophan/chemistry,Glycoproteins/chemistry,Mannose/chemistry,Models, Molecular,Glycosylation,Crystallography, X-Ray,Protein Processing, Post-Translational,Protein Conformation,Databases, Protein,Cryoelectron Microscopy |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Funding Information: | Funder Grant number THE ROYAL SOCIETY URF\R\221006 THE ROYAL SOCIETY RGF\R1\181006 BBSRC (BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL) BB/Y009339/1, BB/Y00888X/1 |
Depositing User: | Pure (York) |
Date Deposited: | 28 Jan 2025 09:50 |
Last Modified: | 06 Feb 2025 00:14 |
Published Version: | https://doi.org/10.1002/pro.70025 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/pro.70025 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222479 |
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Description: Protein Science - 2025 - Holland - Methods for detecting building and improving tryptophan mannosylation in glycoprotein
Licence: CC-BY 2.5