GlycoShape

Phenomenal #glycotime by Meg Lunn-Halbert, Joel Allen and colleagues demonstrates through de novo protein design how steric hindrance controls N-glycan maturation ⬇️ doi.org/10.64898/202... Protein design with RFdiffusionAA coupled with glycosylation with GlycoShape 🧪

Refreshed ReGlyco Filter in bioRxiv 🧪(doi.org/10.64898/202...) in view of the upcoming Protein Design Competition on Monday 28/09 🎉🔥 proteinbase.com/competitions... Each week a new target and if it's a glycoprotein, glycoshape.org and ReGlyco Filter can help screen and optimise your binder design

Pls note that from now on, in case you use tools that require access to an extended dataset (Level 2), we ask you to acknowledge our terms and conditions. Level 2 conformers are under CC BY-NC-ND 4.0 See glycoshape.org/licensing for details

GlycoShape reposted

16 Sept

Fantastic opportunity to talk, listen and discuss the future of #glycotime 🧪 with ECRs and PhD students at the upcoming GRS Glycobiology 2027 organised by the über talented @j-a-n-alexander.bsky.social and @lornamilne.bsky.social who put together a sensational programme. Register asap!! ⬇️

GlycoShape reposted

14 Sept

🚨 Want to be part of top #glycotime on the seaside in the California sunshine? Register to the 2027 GRC Glycobiology ⬇️ Stacy and Lance put togteher up one of the most exciting programmes I have ever seen with phenomenal keynotes! We have 32 abstracts to select, so the next speaker could be YOU! 😎

4 Sept

🚨 New version of GlycoShape is now live at glycoshape.org 🥳 Powered by crabWURCS everything runs on your browser and while you save all you ReGlyco work and go back to it whenever you like 😎 Among other new things: new slick drawer, much easier to use, new slick SNFG representations and new layout

eccb2026.orgCommunities day

4 Sept

We are presenting today some of these new features at the #ECCB2026 workshop eccb2026.org/communities-... at 11 am CEST, contact @glycoexpasy.bsky.social if you would like to attend 👍🧪 #glycotime

GlycoShape reposted

2 Sept

I will be in Geneva at #ECCB2026 for a super #glycotime workshop in glyco-bioinformatics hosted by @glycoexpasy.bsky.social to present a hands-on guide to the new layout and features of @glycoshape.org If you want to hear all about it, just sign up! ⬇️ eccb2026.org/communities-... online and free

GlycoShape reposted

Nick Riley

@nmriley.bsky.social

28 Aug

Replying to @nmriley.bsky.social

We then took a deeper dive into our EpCAM data to look at what integrating bottom-up glycopeptide and intact glycoproteoform measurements can get us, and @emmajays.bsky.social helped us use @glycoshape.org to model how a glycoproteoform with two occupied N-glycosites might look like.

28 Aug

Want to know more about #glycotime resources in bioinformatics and/or build some glycoproteins with GlycoShape? Join us online on Sept 4th for fabulous hands-ON workshops organised by @glycoexpasy.bsky.social 😎🥳🧪 Online registration is FREE (Price: 0 CHF) here, eccb2026.org/communities-...

glycoexpasy.bsky.social@glycoexpasy.bsky.social

Attending @eccb-europe.bsky.social in Geneva this year? Then, you can join our workshop! Programme and registration is here: eccb2026.org/communities-... it's free 🙂 but hurry!

17 July

⬇️ #glycotime 🧪

Elisa Fadda@elisafadda.bsky.social

Isn't it amazing when a fresh new preprint is out on Friday? 😎🥳 Check out the fabulous work by @beatricetropea.bsky.social who gives us a clear mechanistic explanation behind the 'peculiar' structure of the LLO donor preferentially chosen by eukaryotic OST 🤓😍 doi.org/10.64898/202...

doi.orgHow the terminal glucoside of the N-glycan donor affects the catalytic efficiency of the eukaryotic oligosaccharyltransferaseThe eukaryotic oligosaccharyltransferase (OST) is the enzyme responsible for initiating N-glycosylation of secreted proteins by transferring a pre-assembled lipid-linked oligosaccharide (LLO) donor to...

17 July

The fully glucosylated LLO structure is the preferred substrate of eukaryotic OST, especially engineered to enhance N-glycosylation efficiency; but how does that work? and why do we need all those glucoses? @beatricetropea.bsky.social answers all these Q in a new preprint ⬇️ doi.org/10.64898/202...

17 July

Instead of a thread, we have a blog as a tutorial glycoshape.org/blog For any feedback/questions, please feel free to comment below or to quote, we can see both. Happy reading 😎

GlycoShape reposted

2 July

As a fun educational/inspirational #glycotime we decided to curate a Blog on glycoshape.org, you can find it under Resources or here glycoshape.org/blog You can *sign up* to get an email when we post a new entry The latest is E04:Let's talk about glycan binding to viral (glyco)proteins 🧪

30 June

Un-crystallisable glyco-complexes anyone? New work led by John Klassen's lab introduces antibody masking-native mass spectrometry (AM-nMS) a spatially resolved assay that allowed us to map glycan binding sites across the SARS-CoV-2 RBD. The results match our MDs! 😜 All details glycoshape.org/blog

doi.orgLocalizing the Glycan Binding Sites of SARS-CoV-2 Receptor-Binding DomainMapping the binding sites on viral proteins that interact with host glycans is essential for understanding host–pathogen interactions and guiding therapeutic design. While the SARS-CoV-2 spike (S) protein is known to bind host glycans through its N-terminal domain and receptor-binding domain (RBD), the specific glycan-interacting residues on the RBD remain undefined. Here, we introduce antibody masking-native mass spectrometry (AM-nMS), a spatially resolved assay for mapping glycan-binding sites by combining a panel of nanobodies targeting distinct regions within the RBD with center-of-mass monitoring and catch-and-release strategies. Applied to wild-type (Wuhan-Hu-1) SARS-CoV-2 RBD, AM-nMS reveals distinct yet partially overlapping glycan-binding surfaces. Heparan sulfate (HS) oligosaccharides bind within a shallow groove (encompassing residues 420–430, 441–452, and 490–512), which partially overlaps the receptor-binding motif (RBM). Sialylated glycans, including ganglioside oligosaccharides, engage a distal edge of the RBM (residues 470–486 and 490–512) that includes a portion of HS binding groove. Globoside glycans bind at a third site (residues 513–530 and 441–452) that also partially overlaps with the HS-binding region. These multiple binding sites near the RBM enable the RBD to interact with a wide range of host glycans. Site assignments are supported by library screening across the RBD from several SARS-CoV-2 variants of concern (VOCs), competitive binding nMS, mass photometry and molecular dynamics simulations. This work presents the first experimental residue-level map of glycan engagement by the SARS-CoV-2 RBD and establishes AM-nMS as a broadly applicable strategy for localizing glycan-binding sites on proteins.

30 June

link to the paper doi.org/10.1021/acs....

19 June

glycoshape.org has now a blog where we discuss (yep you got it) glycans, glycoproteins and fun stuff! Season 1 is out with: Ep01: Why should we care about glycan heterogeneity? Ep02: How can we include glycan heterogeneity in a 3D framework? Ep03: Molecular precision glycoscience: Enter Siglecs

19 June

At the bottom of the page you'll also find a subscription option where you can sign up for an email notification when a new post is published 🥳

19 June

We are planning to host guest posts 🥳 and we will be very happy to receive suggestions for future posts on topics you would like to read our thoughts on. If you do, pls let us know in the comments ⬇️ Thank you 😎 and happy #glycotime! 🧪

science.orgThe ligand preference of LRP1 is regulated by O-glycansGALNT11-mediated O-glycans modulate LRP1 uptake of tau and Aβ, unveiling glycan-driven mechanisms in neurodegenerative pathways.

Next time you hear 'glycans are just a fancy protein decoration' 😱 show them this fabulous work led by Katrine Schjoldager and team at the CGR 🇩🇰 with us 🇬🇧 showing how The ligand preference of LRP1 is regulated by O-glycans Out now www.science.org/doi/10.1126/... 🧵1/10 ⬇️

9/10 The presence of sialic acid disrupts the contribution of the glycan to the binding to RAP (b). Interestingly the formation of an intramolecular contact between the core1 and Trp63 during O-glycan maturation could potentially affect its sialylation levels by limiting accessibility to ST3GAL1

10/10 Thank you so much to John Hintze (1st author) and to Katrine for her patience and perseverance that lead to this fabulous and comprehensive work. We were really fortunate and happy to contribute with some cool molecular-level insight. Feedback/Questions are more than welcome 😎

science.orgThe ligand preference of LRP1 is regulated by O-glycansGALNT11-mediated O-glycans modulate LRP1 uptake of tau and Aβ, unveiling glycan-driven mechanisms in neurodegenerative pathways.

7/10 But what about the effect of hyposialylation of at C6X(3-5)T*C1 (GALNT11) O-glycans? @silviadandrea.bsky.social ran multiple uncorrelated MD simulations to figure this out using the structure of the RAP/CR5-CR6 complex as a model (PDB 2FYL) with sialylated (and not) core1 at C6-AYP-T-C1

8/10 In the absence of a terminal Sia the Gal of core1 engages in an intramolecular interaction with Trp63 of CR6 (pink in Fig.c and insert), which in turns stabilises the direct contact between the linker and the RAP (red)

science.orgThe ligand preference of LRP1 is regulated by O-glycansGALNT11-mediated O-glycans modulate LRP1 uptake of tau and Aβ, unveiling glycan-driven mechanisms in neurodegenerative pathways.

5/10 SO, does O-glycosylation of CRs influence LRP1 ligand selection and clearance? INDEEDLY it does. O-glycosylation significantly enhances uptake of tau and decreases uptake of Aβ in two cell models, HEK293 and neuroblastoma SH-SY5Y cells ⬇️🤯

6/10 Interestingly the uptake of RAP, A2M, and ApoE ligands were *unchanged* by the O-glycosylation levels of LRP1, suggesting that CRs O-glycosylation modulates selectively LRP1 recognition and linked functions, not all!

science.orgThe ligand preference of LRP1 is regulated by O-glycansGALNT11-mediated O-glycans modulate LRP1 uptake of tau and Aβ, unveiling glycan-driven mechanisms in neurodegenerative pathways.

3/10 LRP1 500-kDa soluble subunit (α) has four ligand-binding cysteine-rich complement type repeats (CRs) clusters (I to IV), with 31 CRs in total target different ligands, such as amyloid-β (Aβ), tau, receptor-associated protein (RAP), alpha-2-macroglobulin (A2M), and apolipoprotein E (ApoE)

4/10 CRs are O-glycosylated at C6X(3-5)T*C1 by GALNT11, one of 20 GalNAc-transferases that initiate protein GalNAc-type O-glycosylation. O-glycans are present at 13 CR linkers in LRP1 and are hyposialylated

science.orgThe ligand preference of LRP1 is regulated by O-glycansGALNT11-mediated O-glycans modulate LRP1 uptake of tau and Aβ, unveiling glycan-driven mechanisms in neurodegenerative pathways.

2/10 Background: LRP1 is a l~600 kDa transmembrane receptor that engages > 50 different ligands for clearance from neuronal and cerebrospinal fluid (CSF). How this broad ligand selection is accomplished and how it leads to different cellular responses is unclear

Glycoheterogeneity is an aspects of glycobiology that most would class into a category between difficult and intolerable, but @benschulz.bsky.social and us love it! So we wrote a whole review in Current Opinion in Structural Biology on it 🧵1/8 ⬇️ doi.org/10.1016/j.sb...

7/8 The reflections and analysis in this review are the product of a lot of conversations and reading through the years, but also of practice by the very talented BIOL6105 students (25/26) who test drove the glycoprotein design protocols for one of their assignments

doi.orgFrom sequence to scaffold: Computational design of protein nanoparticle vaccines from AlphaFold2-predicted building blocks | PNASSelf-assembling protein nanoparticles are being increasingly utilized in the design of next-generation vaccines due to their ability to induce anti...

8/8 Last but not least, big thank YOUs to 1) Syma Khalid @sykhalid.bsky.social for inviting us to write this review for the issue she is editing and to 2) the COSB team, especially Andy Deelen, for their patience, help and support with literally everything!

5/8 On this topic we highly recommend reading the following ** contributions by us and others, Haas et al, doi.org/10.1073/pnas... Debono et al, doi.org/10.1016/j.jb...

doi.orgStructure, sequon recognition and mechanism of tryptophan C-mannosyltransferase - Nature Chemical BiologyTryptophan C-mannosyltransferase (CMT) enzymes append a mannose to the first tryptophan of select sequences, which is important for the trafficking, folding and function of secretory and transmembrane...

6/8 But how can we understand/predict/include glycoheterogeneity in our studies or in the design of glycoprotein biologics? We discuss the hGH design assisted by GlycoShape ⬇️ as an example and recommend the following work when dealing with mucins Chongsaritsinsuk et al, doi.org/10.1038/s414...

3/n On this topic we highly recommend reading the following ** contributions by us and others, Khaleque, Tropea et al, doi.org/10.1101/2025... Bloch et al, doi.org/10.1038/s415...

4/8 Microheterogeneity (a feature not a bug) modulates glycan-dependent structure and function properties with exceptional dynamisms, allowing to tune them as a dial more than a ON/OFF switch, by glycan types conc gradients. This is critical in tuning properties such as immune response

2/8 Macroheretogeneity refers to the occupancy of glycan sites. We discuss how the sequence determinants for N-glycosylation, and not other sequon-dependent PTMs, requires ‘beyond the sequon’ regulation of macroheterogeneity for with direct implications into glycoproteins structure and function

GlycoShape reposted

3 June

🚨 #glycotime seminar alert! June 22nd, 2026 4pm JST (8am BST) @kiyokof.bsky.social will present the GlyTouCan v.4 in the next GlySpace Alliance Seminar event 🔥 If you use @glycoshape.org, you know already aboutGlyTouCan IDs. Tune in ⬇️ to discover what GlyTouCan can do for your research 🥳

2 June

Carbohydrate-binding is a small profit affair, so proteins often adopt complex multidomain architectures enabling a mechanism known as 'binding cooperativity', where binding to one monomer contributes to the binding affinity of the whole systems BUT how does it actually work? 🔥 #glycotime 🧵1/4 ⬇️

3/4 Accordingly the Van’t Hoff analysis shows that this temperature-enhanced cooperativity is predominantly entropy driven, while the overall gain in binding free energy stands regardless of the order in which the monomers are occupied because of the interlocked architecture

2 June

4/4 This work is led by John Klassen and his fabulous group in collaboration with Lara Mahal @glycocode.bsky.social 🥳 and us for the molecular-level insight. As we say, it takes a village to do glycobiology and this one was very exciting, challenging and beautiful! Feedback always welcome 😎

2/4 In this work ⬇️ we used variable temperature native MS in combination with T replica exchange (REMD) to study cholera toxin B subunit pentamer (CTB5) reveal how binding to one monomer (cyan/GM1 yellow) triggers the prestructuring of the next adjacent (purple) doi.org/10.1021/acs....

GlycoShape reposted

7 May

A fab, sunshiny week in 🇩🇰! Great #glycotime 🧪 at the CBM16 in Helsingør, with posters Bea: regulation of N-glycosylation by OST (doi.org/10.1101/2025...) Silvia: Siglec-6 high-recision recognition of glycolipids (doi.org/10.1038/s420...) Ojas: de novo binders design (doi.org/10.64898/202...) 🧵⬇️

24 Apr

Daily job count is quite high these days after the release of our case study 1 week ago and of the ReGlyco de novo Binder Design Filter notebook ⬇️ doi.org/10.64898/202... and res. therein So exciting to see a growing number of researcher including glycosylation in their studies! 🎉 #glycotime 🧪