The DOI matches its Crossref record; 37 of the 42 references it cites were found in a registry or an index.
The Impact of Glycosylation on the Conformational Ensembles of β -, δ -, and γ Sarcoglycans
Open accessPreprint — published as 10.1016/j.bpj.2026.04.018 · Paper page
Abstract
Glycosylation is a pivotal post-translational modification that influences protein folding, stability, and interactions, with direct implications for muscular dystrophy pathogenesis and emerging gene therapies. Sarcoglycans (SGs), β -, δ -, γ -, and α - subunits of the dystrophin–glycoprotein complex (DGC), contain essential N-linked glycosylation sites, and mutations that disrupt glycan attachment, destabilize the complex and cause limb-girdle muscular dystrophy. Yet, the structural consequences of SG glycosylation remain poorly defined due to the absence of experimental sarcoglycan complex structures. Here, we use homology modeling, AlphaFold predictions, and allatom molecular dynamics simulations to probe how N-linked glycans reshape the conformational ensembles of β -, δ -, and γ -SG monomers and the β – δ – γ heterotrimer core. We find that glycosylation increases flexibility and conformational heterogeneity in isolated monomers but reinforces a compact, stabilized architecture in the heterotrimer. Contact map and clustering analyses show that glycans redistribute local residue interactions while preserving global trimer organization, suggesting a context-dependent role in destabilizing monomers yet reinforcing complex stability. These findings provide the first atomistic insight into how glycosylation primes sarcoglycans for assembly and may explain why mutations at glycosylation sites disrupt complex integrity and drive muscular dystrophy phenotypes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Molecular dynamics with coupling to an external bath
Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., & Haak, J. R. (1984) · The Journal of Chemical Physics · doi:10.1063/1.448118 · Cited by 30,700 · cited 1×
“…simulations, we used the standard input file for NPT simulations generated by CHARMM-GUI, with temperature control using the Langevin thermostat 27 with a friction coefficient of 1.0 ps − 1 and semi-isotropic pressure control using the Berendsen barostat 28 with a relaxation time of 1.0 ps.”
InfluentialParticle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems
Darden, T., York, D., & Pedersen, L. (1993) · The Journal of Chemical Physics · doi:10.1063/1.464397 · Cited by 30,546 · cited 1×
“22 The effects of long-range van der Waals interactions were estimated using a dispersion correction model.”
SWISS-MODEL: homology modelling of protein structures and complexes
Waterhouse, A. M., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F. T., de Beer, T., Rempfer, C., Bordoli, L., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky427 · Cited by 13,364 · cited 1×
“14,15 To mimic the in vitro environment, all structures, whether as a monomeric or heterotrimeric system, were integrated into a DMPC bi-layer membrane (1,2-dimyristoyl-sn-glycero-3-phosphocholine).”
CHARMM‐GUI: A web‐based graphical user interface for CHARMM
Jo, S., Kim, T., Iyer, V. G., & Im, W. (2008) · Journal of Computational Chemistry · doi:10.1002/jcc.20945 · Cited by 9,284 · cited 1×
“17,18 Simulations were prepared with the CHARMM-GUI server, 19,20 and each subunit was oriented according to the Orientations of Proteins in Mem-branes (OPM) database, 21 with standard N-and C-terminal patches applied.”
CHARMM36m: an improved force field for folded and intrinsically disordered proteins
Huang, J., Rauscher, S., Nawrocki, G., Ran, T., Feig, M., de Groot, B. L., Grubmüller, H., & MacKerell, A. D. (2016) · Nature Methods · doi:10.1038/nmeth.4067 · Cited by 7,334
Lee, J., Cheng, X., Swails, J., Yeom, M. S., Eastman, P. K., Lemkul, J. A., Wei, S., Buckner, J., Jeong, J. C., Qi, Y., et al. (2015) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.5b00935 · Cited by 4,390 · cited 1×
“23,24 Then, 20 independent 100 ns production runs were performed using the GPU-accelerated CUDA 25 version of AMBER18, pmemd.”
Varadi, M., Bertoni, D., Magana, P., Paramval, U., Pidruchna, I., Radhakrishnan, M., Tsenkov, M., Nair, S., Mirdita, M., Yeo, J., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad1011 · Cited by 2,052 · cited 1×
“Guided by these homologs, the amino acid sequences of β -, δ -, and γ -sarcoglycans were extracted from UniProt 11 (see Table S1) and modeled as both monomers and a heterotrimer using AlphaFold 12,13 and homology modeling via the SWISS-MODEL server.”
Loughnan, A. (2019) · Self, Others and the State · doi:10.1017/9781108596367.008 · Cited by 1,719 · cited 2×
“17,18 Simulations were prepared with the CHARMM-GUI server, 19,20 and each subunit was oriented according to the Orientations of Proteins in Mem-branes (OPM) database, 21 with standard N-and C-terminal patches applied.”
CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes.
Jo, S., Lim, J. B., Klauda, J. B., & Im, W. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.04.013 · Cited by 1,674 · cited 1×
“17,18 Simulations were prepared with the CHARMM-GUI server, 19,20 and each subunit was oriented according to the Orientations of Proteins in Mem-branes (OPM) database, 21 with standard N-and C-terminal patches applied.”
Research works printed but not linked: 6
- 10.1074/jbc.273.52.34667 · DOI
- 10.1038/s41586-024-08310-2 · DOI
- 10.1093/nar/gky092 · DOI
- 10.1016/j.bpj.2015.11.3431 · DOI
- 2008, Scalable parallel programming with cuda: Is cuda the parallel programming model that application developers have been waiting for?, Queue, 6, 40, 10.1145/1365490.1365500 · DOI
- 1996, others Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation, American journal of human genetics, 59, 1040
Metadata
- Authors
- Fazelpour, E., Cook, G. A., & McCullagh, M.
- Affiliations
- Oklahoma State University (US)
- Corresponding author
- McCullagh, Martin
- Venue
- Biophysical Journal
- Publisher
- openRxiv
- Published
- 2026-01-14
- Volume
- 125
- Issue
- 11
- Pages
- 2657-2669
- ISSN
- 0006-3495 (ISSN-L)
- PMC
- PMC13294987
- OpenAlex
- W7155102384
- Cited by
- 0
- References
- 42
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biophysical Journal (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, cc-by-nd)
- Funders
- National Science Foundation (1531128)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01AI166050)
- Oklahoma State University (OAC-1531128)
- National Institute of Allergy and Infectious Diseases (R01AI166050)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- sarcoglycans, glycosylation, N-glycans, dystrophin-glycoprotein complex, limb-girdle muscular dystrophy, conformational ensembles, protein flexibility, glycosylation site mutations
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: The Impact of Glycosylation on the Conformational Ensembles of β -, δ -, and γ Sarcoglycans. https://app.cochat.ai/papers/10.64898/2026.01.13.699269
- The paper
- Fazelpour, E., Cook, G. A., & McCullagh, M. (2026). The Impact of Glycosylation on the Conformational Ensembles of β -, δ -, and γ Sarcoglycans. Biophysical Journal. https://doi.org/10.64898/2026.01.13.699269
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
