Glycosylation of viral surface proteins probed by mass spectrometry

Hargett, Audra A.; Renfrow, Matthew B.

doi:10.1016/j.coviro.2019.05.003

Cited by 31 publications

(19 citation statements)

References 101 publications

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“…The viral enzyme purifies with tightly bound NAD(H), and it can function on either dTDP‐ d ‐glucose or UDP‐ d ‐glucose. It is well known that most conventional viruses utilize host cellular glycosylation pathways to modify their proteins . The fact that the Mimivirus genome, as well as those of other giant viruses, encodes enzymes involved in nucleotide‐linked sugar metabolism is, indeed, fascinating .…”

Section: Discussionmentioning

confidence: 99%

Biochemical analysis of a sugar 4,6‐dehydratase from Acanthamoeba polyphaga Mimivirus

2020

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The exciting discovery of the giant DNA Mimivirus in 2003 challenged the conventional description of viruses in a radical way, and since then, dozens of additional giant viruses have been identified. It has now been demonstrated that the Mimivirus genome encodes for the two enzymes required for the production of the unusual sugar 4-amino-4,6-dideoxy-D-glucose, namely a 4,6-dehydratase and an aminotransferase. In light of our long-standing interest in the bacterial 4,6-dehydratases and in unusual sugars in general, we conducted a combined structural and functional analysis of the Mimivirus 4,6-dehydratase referred to as R141. For this investigation, the threedimensional X-ray structure of R141 was determined to 2.05 Å resolution and refined to an R-factor of 18.3%. The overall fold of R141 places it into the short-chain dehydrogenase/reductase (SDR) superfamily of proteins. Whereas its molecular architecture is similar to that observed for the bacterial 4,6-dehydratases, there are two key regions where the polypeptide chain adopts different conformations. In particular, the conserved tyrosine that has been implicated as a catalytic acid or base in SDR superfamily members is splayed away from the active site by nearly 12 Å, thereby suggesting that a major conformational change must occur upon substrate binding. In addition to the structural analysis, the kinetic parameters for R141 using either dTDP-D-glucose or UDP-D-glucose as substrates were determined. Contrary to a previous report, R141 demonstrates nearly identical catalytic efficiency with either nucleotide-linked sugar. The data presented herein represent the first threedimensional model for a viral 4,6-dehydratase and thus expands our understanding of these fascinating enzymes. K E Y W O R D SAcanthamoeba polyphaga Mimivirus, dideoxysugar, giant viruses, UDP-D-glucose 4,6-dehydratase, UDP-D-viosamine, viral glycans, X-ray structure Abbreviations: dTDP, thymidine diphosphate; ESI, electrospray ionization; HEPES, N-2-hydroxyethylpiperazine-N 0 -2-ethanesulfonic acid; HEPPS, N-2-hydroxyethylpiperazine-N 0 -3-propanesulfonic acid; HPLC, high-performance liquid chromatography; NAD + , nicotinamide adenine dinucleotide (oxidized); NADH, nicotinamide adenine dinucleotide (reduced); NADP + , nicotinamide adenine dinucleotide phosphate (oxidized); NADPH, nicotinamide adenine dinucleotide phosphate (reduced); Ni-NTA, nickel-nitrilotriacetic acid; PCR, polymerase chain reaction; PLP, pyridoxal 5 0 -phosphate; Qui4N, 4-amino-4,6-dideoxy-D-glucose; TEV, Tobacco Etch Virus; Tris, tris-(hydroxymethyl)aminomethane; UDP, uridine diphosphate.

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Section: Discussionmentioning

confidence: 99%

Biochemical analysis of a sugar 4,6‐dehydratase from Acanthamoeba polyphaga Mimivirus

2020

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“…In addition, replication of the same virus in different cells can generate different glycosylation, which severely affects the transmission ability of the virus ( 56 ). For example, HIV from different cell lines has different glycosylation in its envelope proteins, and the glycosylation difference affects its interaction with Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN).…”

Section: Glycans Of Viral Proteins and Their Functionsmentioning

confidence: 99%

The Importance of Glycans of Viral and Host Proteins in Enveloped Virus Infection

Liu

Wang

et al. 2021

Front. Immunol.

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Animal viruses are parasites of animal cells that have characteristics such as heredity and replication. Viruses can be divided into non-enveloped and enveloped viruses if a lipid bilayer membrane surrounds them or not. All the membrane proteins of enveloped viruses that function in attachment to target cells or membrane fusion are modified by glycosylation. Glycosylation is one of the most common post-translational modifications of proteins and plays an important role in many biological behaviors, such as protein folding and stabilization, virus attachment to target cell receptors and inhibition of antibody neutralization. Glycans of the host receptors can also regulate the attachment of the viruses and then influence the virus entry. With the development of glycosylation research technology, the research and development of novel virus vaccines and antiviral drugs based on glycan have received increasing attention. Here, we review the effects of host glycans and viral proteins on biological behaviors of viruses, and the opportunities for prevention and treatment of viral infectious diseases.

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“…High viral glycan density and local protein architecture can sterically impair the glycan maturation pathway. Impaired glycan maturation resulting in the presence of oligomannose-type glycans can be a sensitive reporter of nativelike protein architecture (8), and site-specific glycan analysis can be used to compare different immunogens and monitor manufacturing processes (18). Additionally, glycosylation can influence the trafficking of recombinant immunogen to germinal centers (19).…”

mentioning

confidence: 99%

Site-specific glycan analysis of the SARS-CoV-2 spike

Watanabe

Allen

Wrapp

et al. 2020

Science

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The emergence of the betacoronavirus, SARS-CoV-2, the causative agent of COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycanprocessing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.

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Glycosylation of viral surface proteins probed by mass spectrometry

Cited by 31 publications

References 101 publications

Biochemical analysis of a sugar 4,6‐dehydratase from Acanthamoeba polyphaga Mimivirus

Biochemical analysis of a sugar 4,6‐dehydratase from Acanthamoeba polyphaga Mimivirus

The Importance of Glycans of Viral and Host Proteins in Enveloped Virus Infection

Site-specific glycan analysis of the SARS-CoV-2 spike

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