A Necessary and Sufficient Determinant for Protein-selective Glycosylation in Vivo

Miller, Erin; Fiete, Dorothy; Blake, Nicquet M.J.; Beranek, Mary C.; Oates, Edward L.; Mi, Yiling; Roseman, Daniel S.; Baenziger, Jacques U.

doi:10.1074/jbc.m708160200

Cited by 28 publications

(28 citation statements)

References 49 publications

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“…The group of Jacques Baenziger could provide evidence that for the activity of ␤4-specific GalNAc transferases ␤GT3 and ␤GT4, a 19-meric peptide sequence within the target protein (LRRFIEQKITKRKKEKYWP) is necessary and sufficient (11). This determining cis-located peptide is characterized by a high content of basic amino acids and an ␣-helical structure.…”

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confidence: 99%

O-Linked N,N′-Diacetyllactosamine (LacdiNAc)-modified Glycans in Extracellular Matrix Glycoproteins Are Specifically Phosphorylated at Subterminal N-Acetylglucosamine

Breloy

Pacharra

Ottis

et al. 2012

Journal of Biological Chemistry

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confidence: 99%

O-Linked N,N′-Diacetyllactosamine (LacdiNAc)-modified Glycans in Extracellular Matrix Glycoproteins Are Specifically Phosphorylated at Subterminal N-Acetylglucosamine

Breloy

Pacharra

Ottis

et al. 2012

Journal of Biological Chemistry

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“…Factors that influence the type of carbohydrate chain that is attached at any one N-linked site are the accessibility of the carbohydrate chain to processing enzymes (49), protein sequences surrounding the site (5,40), and the type of cell from which the protein is produced (19).…”

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confidence: 99%

Fundamental Difference in the Content of High-Mannose Carbohydrate in the HIV-1 and HIV-2 Lineages

Stansell

Desrosiers

2010

J Virol

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The virus-encoded envelope proteins of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) typically contain 26 to 30 sites for N-linked carbohydrate attachment. N-linked carbohydrate can be of three major types: high mannose, complex, or hybrid. The lectin proteins from Galanthus nivalis (GNA) and Hippeastrum hybrid (HHA), which specifically bind high-mannose carbohydrate, were found to potently inhibit the replication of a pathogenic cloned SIV from rhesus macaques, SIVmac239. Passage of SIVmac239 in the presence of escalating concentrations of GNA and HHA yielded a lectin-resistant virus population that uniformly eliminated three sites (of 26 total) for N-linked carbohydrate attachment (Asn-X-Ser or Asn-X-Thr) in the envelope protein. Two of these sites were in the gp120 surface subunit of the envelope protein (Asn244 and Asn460), and one site was in the envelope gp41 transmembrane protein (Asn625). Maximal resistance to GNA and HHA in a spreading infection was conferred to cloned variants that lacked all three sites in combination. Variant SIV gp120s exhibited dramatically decreased capacity for binding GNA compared to SIVmac239 gp120 in an enzyme-linked immunosorbent assay (ELISA). Purified gp120s from six independent HIV type 1 (HIV-1) isolates and two SIV isolates from chimpanzees (SIVcpz) consistently bound GNA in ELISA at 3-to 10-fold-higher levels than gp120s from five SIV isolates from rhesus macaques or sooty mangabeys (SIVmac/sm) and four HIV-2 isolates. Thus, our data indicate that characteristic high-mannose carbohydrate contents have been retained in the cross-species transmission lineages for SIVcpz-HIV-1 (high), SIVsm-SIVmac (low), and SIVsm-HIV-2 (low).The envelope proteins of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) are heavily glycosylated. N-linked carbohydrate is attached to the nascent protein at the asparagine of the consensus sequence N-X-S or N-X-T, where X is any amino acid except a proline (31,52,53). The number of potential N-linked carbohydrate attachment sites in the surface subunit of Env (gp120) ranges from 18 to 33, with a median of 25 (34, 65). There are typically 3 or 4 potential N-linked sites in the ectodomain of the Env transmembrane protein (gp41) (34).N-linked glycosylation of a protein consists of the en bloc transfer of the carbohydrate core oligosaccharide (two N-acetylglucosamines, nine mannoses, and three glucoses) from dolichol to the asparagine of the N-linked attachment site (8, 60). Initially the attached carbohydrate is processed into the high-mannose type (8). In the Golgi complex, high-mannose carbohydrate may be further processed into complex or hybrid oligosaccharides (58). Incomplete processing of N-linked carbohydrate results in the production of high-mannose carbohydrate chains, which terminate in mannose (58). Fully processed complex carbohydrate chains terminate in galactose, N-acetylglucosamine, sialic acid, or glucose (33, 57). Hybrid carbohydrate chains have two branches from the core, one tha...

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“…Native mammalian proteins that contain glycans with LacdiNAc also show a similar glycosylation profile when produced in kidney cell lines (345)(346)(347). Several studies suggest that protein sequences proximal to putative N-linked sites act as cis-regulatory elements for β4-specific GalNAc-transferases (345,346,351,353). One such study identified the 19 amino acid peptide LRRFIEQKITKRKKEKYMP displaying an alpha-helical structure at carboxyl-terminus of CA6 (346).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike β4Gal-Ts, the catalytic efficiencies of β4GalNAc-Ts are dependent on the protein, indicating that specific protein recognition determinants drive LacdiNAc addition (356). Native mammalian proteins that contain glycans with LacdiNAc also show a similar glycosylation profile when produced in kidney cell lines (345)(346)(347). Several studies suggest that protein sequences proximal to putative N-linked sites act as cis-regulatory elements for β4-specific GalNAc-transferases (345,346,351,353).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies suggest that protein sequences proximal to putative N-linked sites act as cis-regulatory elements for β4-specific GalNAc-transferases (345,346,351,353). One such study identified the 19 amino acid peptide LRRFIEQKITKRKKEKYMP displaying an alpha-helical structure at carboxyl-terminus of CA6 (346). This 19-residue peptide promoted LacdiNAc extensions on CA6.…”

Section: Discussionmentioning

confidence: 99%

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Structural characterisation of glycosylation of paramyxovirus attachment and fusion proteins by mass spectrometry

Pegg¹

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The family Paramyxoviridae (paramyxovirus) contains several significant human and animal pathogens.Represented within this family are human respiratory syncytial virus (hRSV) and Newcastle disease virus (NDV). The former contributes significantly to severe respiratory tract disease in infants, children and immunocompromised individuals. At present, highly efficacious therapeutics or safe and effective vaccines are not available for hRSV. NDV is the causative agent of Newcastle disease, afflicting a wide range of avian species. The desire to study NDV is due not only to the significant economic impact it has on the poultry industry worldwide, but also its potential use as an oncolytic agent and vaccine vector in humans and animals. Additionally, findings on NDV may be translated to closely related viruses that cause disease in humans, such as parainfluenza viruses.As outlined in Chapter 1 of this thesis, the infectious processes of all members of this family are driven by two major membrane glycoproteins whose ectodomains project from the viral envelope: the fusion (F) and attachment glycoproteins. The F glycoprotein is responsible for viral entry by means of fusion with host cell membranes while the variable attachment glycoproteins, haemagglutinin, haemagglutininneuraminidase (HN) and major surface glycoprotein (G), are involved in viral attachment to host cells.Previous studies have shown that altering the glycosylation profile of these proteins can modulate the ability of the virus to infect host cells and stimulate the host immune system. As yet, site-specific glycan heterogeneity of hRSV and NDV surface glycoproteins has not been defined at a chemical level. As described in Chapter 2, reverse-phase liquid chromatography tandem mass spectrometry (MS) strategies were implemented to characterise intact glycopeptides from the attachment and F glycoproteins of hRSV and NDV. Site-occupancy and monosaccharide compositions at a given site were determined using collision-induced dissociation, higher-energy collision dissociation, electron-transfer dissociation and electron-transfer dissociation combined with collision dissociation. As described in Chapter 3, a spectral processing program was developed called OxoExtract to aid identification of intact glycopeptides that were fragmented with higher-energy collision dissociation.The F and HN proteins of NDV were derived from virions propagated in embryonic eggs. Analyses of HN in Chapter 4 revealed high mannose N-linked glycans and complex or hybrid N-linked glycans that were variably fucosylated, sialylated and sulfated or phosphorylated. In total 63, 58, and 37 glycans were identified at sites N341, N433 and N481, respectively. In addition, a previously undocumented Olinked glycosylation site was identified in the stalk domain of the protein. Observed glycans from NDV F described in Chapter 5 were mainly high mannose, containing variations of five to nine mannose ii residues across four sites, N85, N191, N366 and N471. There was also evidence of fucosylated c...

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A Necessary and Sufficient Determinant for Protein-selective Glycosylation in Vivo

Cited by 28 publications

References 49 publications

O-Linked N,N′-Diacetyllactosamine (LacdiNAc)-modified Glycans in Extracellular Matrix Glycoproteins Are Specifically Phosphorylated at Subterminal N-Acetylglucosamine

O-Linked N,N′-Diacetyllactosamine (LacdiNAc)-modified Glycans in Extracellular Matrix Glycoproteins Are Specifically Phosphorylated at Subterminal N-Acetylglucosamine

Fundamental Difference in the Content of High-Mannose Carbohydrate in the HIV-1 and HIV-2 Lineages

Structural characterisation of glycosylation of paramyxovirus attachment and fusion proteins by mass spectrometry

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