Communication: Folding of glycosylated proteins under confinement

Shental-Bechor, Dalit; Levy, Yaakov

doi:10.1063/1.3650700

Cited by 10 publications

(11 citation statements)

References 20 publications

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“…We observed that while order-promoting residues are equivalently distributed between N-linked glycosites and control ordered regions, the former are relatively further depleted of disorder-promoting residues compared to the latter. N-glycans have been shown through mounting theoretical 26,50 and experimental 51 evidence to impact the folding and structure of glycoproteins (although the relationship is not always positively regulatory) 52,53 . The triose core of N-glycoproteins enhances both the kinetics and stability of tertiary glycoprotein folds 54 .…”

Section: Discussionmentioning

confidence: 99%

Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins

Goutham¹,

Kumari

Pally³

et al. 2020

Sci Rep

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Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions. However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of n-linked glycosylations or n-glycosites, to be predominantly present in the regions of predicted order. When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans. We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures. When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures. N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions. our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of n-glycosite neighborhoods and disordered stretches.One of the common co-and post-translational modifications of polypeptides is the conjugation of branched glycosylations to asparagines (known as N-linked glycosylations) 1 . N-linked glycosylation begins with the assembly of an oligosaccharide on dolichol pyrophosphate and the subsequent transfer of the oligosaccharide to the asparagine residues of polypeptides in the lumen of the endoplasmic reticulum; the oligosaccharide is further remodeled in the Golgi complex. Several proteins that end up in the extracellular milieu or as transmembrane proteins are N-linked glycoconjugates. The establishment of organismal morphologies has been sought to be understood through the interactions of a highly conserved set of proteins known as the developmental genetic toolkit 2 . Most toolkit proteins, which are involved in tissue-scale processes, such as cell-cell and cell-matrix adhesion, diffusion-driven signaling and cell movement, are extracellular-or membrane-bound glycoproteins 3,4 . The fundamental role of such toolkit proteins in mechanisms of organ-and organismal-development across diverse clades suggests evolutionary constraints on their structures and folds, while they may have continued to evolve to perform newer functions as organisms occupied and constructed newer niches.A large number of eukaryotic pro...

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Section: Discussionmentioning

confidence: 99%

Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins

Goutham¹,

Kumari

Pally³

et al. 2020

Sci Rep

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“…These effects demonstrate that glycosylation affects the protein energy landscape, and it has been suggested that protein stabilization by glycosylation may be due to an enthalpic effect resulting from interactions between the protein and the attached glycans (17,20,21). In silico studies using coarsegrained strategies corroborate the enthalpic stabilization of the Src-SH3 domain by different degrees of glycosylation (22). In contrast, other studies suggest that the stabilization might be due either to a "chaperone-like" activity of glycans (14,17) or to hydrophobic collapse resulting from impaired solvation of the protein (23) and is largely entropic in origin (14,17).…”

mentioning

confidence: 49%

Engineering the Pattern of Protein Glycosylation Modulates the Thermostability of a GH11 Xylanase

Fonseca-Maldonado

Vieira

Alponti

et al. 2013

Journal of Biological Chemistry

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Background: The molecular basis of increased protein stability by N-glycosylation is incompletely understood. Results: Glycosylation position rather than number is more important for protein thermostability in the xylanase A from Bacillus subtilis. Conclusion: Glycans contribute both to stabilizing protein-glycan and less favorable glycan-glycan interactions. An extensive protein-glycan interface favors protein stability. Significance: Formation of a protein-glycan interface provides a conceptual framework to understand glycoprotein stabilization.

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“…These results suggest that the covalent immobilization of BOD in GO produced a reduction in protein dynamics by virtue of the covalent bond, while the adsorbed protein had a more dynamical structure. The confinement produced by GO can also modulate the biophysical and structural features of proteins [ 44 ]. This confinement can also be found inside the cell, where chaperonins produce a “cage effect” to facilitating protein folding, thereby helping them to reach their functional conformation [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Graphene oxide as a protein matrix: influence on protein biophysical properties

et al. 2015

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BackgroundThis study provides fundamental information on the influence of graphene oxide (GO) nanosheets and glycans on protein catalytic activity, dynamics, and thermal stability. We provide evidence of protein stabilization by glycans and how this strategy could be implemented when GO nanosheets is used as protein immobilization matrix. A series of bioconjugates was constructed using two different strategies: adsorbing or covalently attaching native and glycosylated bilirubin oxidase (BOD) to GO.ResultsBioconjugate formation was followed by FT-IR, zeta-potential, and X-ray photoelectron spectroscopy measurements. Enzyme kinetic parameters (km and kcat) revealed that the substrate binding affinity was not affected by glycosylation and immobilization on GO, but the rate of enzyme catalysis was reduced. Structural analysis by circular dichroism showed that glycosylation did not affect the tertiary or the secondary structure of BOD. However, GO produced slight changes in the secondary structure. To shed light into the biophysical consequence of protein glycosylation and protein immobilization on GO nanosheets, we studied structural protein dynamical changes by FT-IR H/D exchange and thermal inactivation.ConclusionsIt was found that glycosylation caused a reduction in structural dynamics that resulted in an increase in thermostability and a decrease in the catalytic activity for both, glycoconjugate and immobilized enzyme. These results establish the usefulness of chemical glycosylation to modulate protein structural dynamics and stability to develop a more stable GO-protein matrix.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0134-0) contains supplementary material, which is available to authorized users.

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Communication: Folding of glycosylated proteins under confinement

Cited by 10 publications

References 20 publications

Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins

Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins

Engineering the Pattern of Protein Glycosylation Modulates the Thermostability of a GH11 Xylanase

Graphene oxide as a protein matrix: influence on protein biophysical properties

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