A post-translational modification of human Norovirus capsid protein attenuates glycan binding

Mallagaray, Álvaro; Creutznacher, Robert; Dülfer, Jasmin; Mayer, P; Grimm, Lena Lisbeth; Orduña, Jose Maria; Trabjerg, Esben; Stehle, Thilo; Rand, Kasper D.; Blaum, Bärbel S.; Uetrecht, Charlotte; Peters, Thomas

doi:10.1038/s41467-019-09251-5

Cited by 52 publications

(181 citation statements)

References 75 publications

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“…Using a freshly purified sample of NN P dimers we obtained a K D value of 5.6 m m (cf. Figure ), in excellent agreement with the value of 5.5 m m from a competition STD NMR experiment …”

Section: Resultssupporting

confidence: 86%

“…Our experiments show that binding of bile acids to the low‐affinity site and binding of HBGAs to the HBGA site are independent events. Likewise, we have shown that the influence of spontaneous deamidation in the HBGA binding site on the binding affinity for bile acids is negligible. These findings suggest that there is no or very minor cross‐talk between these binding events.…”

Section: Discussionmentioning

confidence: 62%

“…For GII.4 Saga P dimers it has been shown that spontaneous deamidation of Asn373 and subsequent formation of an isoaspartate residue at this position abrogates HBGA binding . This process is likely to be relevant for about 66 % of all GII.4 strains.…”

Section: Resultsmentioning

confidence: 99%

“…However, the observation of similar binding affinities of various NoV strains (Table ) indirectly suggests similar binding modes and sites in all cases. A structure based sequence alignment of NoV VP1 domains available from our previous study shows that within a given genotype most amino acid positions are highly conserved. Therefore, it is not surprising that some of the amino acids identified to be affected by bile acid binding are also highly conserved.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we obtained a nearly complete backbone assignment of the P‐domain of a human epidemic genotype norovirus, GII.4 Saga . We also obtained a complete methyl group assignment of a MILVA‐labeled sample of GII.4 Saga P‐domain (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

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Chemical‐Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

et al. 2019

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Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low‐affinity bile acid binding site of a human GII.4 NoV strain. Long‐timescale MD simulations reveal the formation of a ligand‐accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo‐blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus‐like particles of seven different strains suggest that low‐affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.

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“…Using a freshly purified sample of NN P dimers we obtained a K D value of 5.6 m m (cf. Figure ), in excellent agreement with the value of 5.5 m m from a competition STD NMR experiment …”

Section: Resultssupporting

confidence: 86%

Section: Discussionmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chemical‐Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

et al. 2019

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How Isomerization and Epimerization in Long‐Lived Proteins Affect Lysosomal Degradation and Proteostasis

Julian¹

2021

Long‐lived Proteins in Human Aging and Disease

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Evolutionary Spread of Distinct O‐methyltransferases Guides the Discovery of Unique Isoaspartate‐Containing Peptides, Pamtides

Lee,

Park,

Kim

et al. 2023

Advanced Science

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Ribosomally synthesized and post‐translationally modified peptides (RiPPs) are a structurally diverse class of natural products with a distinct biosynthetic logic, the enzymatic modification of genetically encoded precursor peptides. Although their structural and biosynthetic diversity remains largely underexplored, the identification of novel subclasses with unique structural motifs and biosynthetic pathways is challenging. Here, it is reported that peptide/protein L‐aspartyl O‐methyltransferases (PAMTs) present in several RiPP subclasses are highly homologous. Importantly, it is discovered that the apparent evolutionary transmission of the PAMT gene to unrelated RiPP subclasses can serve as a basis to identify a novel RiPP subclass. Biochemical and structural analyses suggest that homologous PAMTs convert aspartate to isoaspartate via aspartyl‐O‐methyl ester and aspartimide intermediates, and often require cyclic or hairpin‐like structures for modification. By conducting homology‐based bioinformatic analysis of PAMTs, over 2,800 biosynthetic gene clusters (BGCs) are identified for known RiPP subclasses in which PAMTs install a secondary modification, and over 1,500 BGCs where PAMTs function as a primary modification enzyme, thereby defining a new RiPP subclass, named pamtides. The results suggest that the genome mining of proteins with secondary biosynthetic roles can be an effective strategy for discovering novel biosynthetic pathways of RiPPs through the principle of “guilt by association”.

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A post-translational modification of human Norovirus capsid protein attenuates glycan binding

Cited by 52 publications

References 75 publications

Chemical‐Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Chemical‐Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

How Isomerization and Epimerization in Long‐Lived Proteins Affect Lysosomal Degradation and Proteostasis

Evolutionary Spread of Distinct O‐methyltransferases Guides the Discovery of Unique Isoaspartate‐Containing Peptides, Pamtides

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