Glycoprotein Folding in the Endoplasmic Reticulum

Benham, Adam M.; Braakman, Ineke

doi:10.1080/10409230091169258

Cited by 14 publications

(14 citation statements)

References 281 publications

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“…The N-linked carbohydrates, which are exposed luminally in cellular organelles during synthesis, are not likely to be involved in a direct binding to the p27 component of the RNP, considering the role of S in HDV RNP envelopment. In fact, the removal of carbohydrates on the HBV envelope proteins may have various consequences, including a modification in their interaction with molecular chaperones and lectins, resulting in an alteration of their intracellular trafficking (1,26). However, in the case of ngS, we did not observe any inhibition of secretion as measured by metabolic labeling and pulse-chase analysis (data not shown); the kinetic of ngS secretion as subviral particles was equivalent to that of the wt.…”

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confidence: 63%

Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus

Sureau

Fournier‐Wirth

Maurel

2003

J Virol

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Hepatitis delta virus (HDV) particles are coated with the large (L), middle (M), and small (S) hepatitis B virus envelope proteins. In the present study, we constructed glycosylation-defective envelope protein mutants and evaluated their capacity to assist in the maturation of infectious HDV in vitro. We observed that the removal of N-linked carbohydrates on the S, M, and L proteins was tolerated for the assembly of subviral hepatitis B virus (HBV) particles but was partially inhibitory for the formation of HDV virions. However, when assayed on primary cultures of human hepatocytes, virions coated with S, M, and L proteins lacking N-linked glycans were infectious. Furthermore, in the absence of M, HDV particles coated with nonglycosylated S and L proteins retained infectivity. These results indicate that carbohydrates on the HBV envelope proteins are not essential for the in vitro infectivity of HDV.Hepatitis delta virus (HDV), in association with the helper hepatitis B virus (HBV), causes acute and chronic infections which may eventually develop into cirrhosis and liver cancer in humans (6,30). HDV is considered a satellite of HBV because it depends on the latter for the supply of envelope proteins that are essential for virion assembly (4). The HDV genome is a single-stranded circular RNA that encodes the small (p24) and large (p27) forms of the HDV antigen (HDAg) protein, but it lacks the coding capacity for envelope proteins. The HDV particle consists of an outer envelope of HBV origin and an inner ribonucleoprotein (RNP) made of the genomic HDV RNA and the HDV-encoded p24 and p27 delta proteins. Similar to that of HBV, the HDV envelope consists of a lipid membrane in which multiple copies of the three HBV surface proteins, designated large (L), middle (M), and small (S), are anchored. L, M, and S are encoded by a single open reading frame on the HBV genome, and they are translated from different in-frame start codons to a common stop codon (24). The L protein contains three distinct regions: the N-terminal pre-S1, the central pre-S2, and the C-terminal S regions. The M protein includes the pre-S2 and S regions, and S consists of the S domain only, but it is the most abundantly expressed (Fig. 1).A peculiar feature of the S protein is its ability to assemble empty (subviral) particles, which are secreted in large excess compared with the number of mature virions. Synthesis occurs at the endoplasmic reticulum membrane, and particles are formed by the budding of envelope protein aggregates into the lumen of a postendoplasmic reticulum/pre-Golgi cellular compartment (16). Transport to the extracellular space is thought to follow the constitutive secretion pathway. In addition to their capacity for subviral particle formation, singly expressed S proteins can envelop the HDV RNPs, leading to the formation of particles that are structurally identical to mature HDV but are functionally impaired (noninfectious) in the absence of L (31,32,34). In contrast, the HBV nucleocapsid envelopment requires the presence of L ...

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confidence: 63%

Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus

Sureau

Fournier‐Wirth

Maurel

2003

J Virol

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“…In specific cases, data available from mammalian systems also will be included in the discussion. However, a detailed review on either the yeast or the mammalian secretion pathway is beyond the scope of this paper and can be found elsewhere (Lazar et al, 1997;Sakaguchi, 1997;Zapun et al, 1999;Benham and Braakman, 2000).…”

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confidence: 99%

The Secretion Pathway in Filamentous Fungi: A Biotechnological View

Conesa¹,

Punt²,

Luijk³

et al. 2001

Fungal Genetics and Biology

226

152

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“…1) and may be required to maintain the intra-and interdomain structure integrity. It is known that the misfolded proteins are usually retained and degraded inside the cells (41). Residues Gln 97 and Phe 98 are involved in linking the EGF-2 domain to the catalytic domain by making hydrophobic interactions with the hydrophobic patch formed by residues cY128, cY130, and cF133 (chymotrypsin numbering) of the catalytic domain (42).…”

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confidence: 99%

Identification of Functionally Important Residues of the Epidermal Growth Factor-2 Domain of Factor IX by Alanine-scanning Mutagenesis

Chang

Hamaguchi

et al. 2002

Journal of Biological Chemistry

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This paper describes the consequences of alaninescanning mutagenesis on 28 positions of the second epidermal growth factor (EGF-2) domain of factor IX. We identified four positions of Gln 97 , Phe 98 , Tyr 115 , and Leu 117 that are critical for secretion of factor IX. Of the remaining mutations, 4 mutants (V86A, E113A, K122A, and S123A) are as active as wild-type factor IX (IXwt); 16 (D85A, K100A, N101A, D104A, N105A, R116A, E119A, T87A, I90A, K91A, R94A, E96A, S102A, K106A, T112A, and N120A) retain reduced but detectable activity, and 4 (N89A, N92A, G93A, and V107A) are nearly inert in the clotting assay. Both factor XIa and the factor VIIa-tissue factor complex effectively catalyzed the activation of these mutants except N89A. The mutant V107A failed to form the factor tenase complex with factor VIIIa because of a 35-fold increase in K d . The mutants N89A and N92A did not compete with factor IXwt for factor VIIIa binding, and G93A exhibited a 6-fold increase in K i values in the competitive binding assay. It appears that mutations at these positions have significantly affected the interaction between factor IX and factor VIIIa, although other mutations had little effect on the binding of factor IX to factor VIIIa. Mutations in two regions, Thr 87 -Gly 93 and Asn 101 -Val 107 , significantly increased the K m value of factor IXa (2-10-fold) in cleavage of factor X in the absence of factor VIIIa. In the presence of factor VIIIa, the catalytic efficiency of each mutant toward factor X paralleled its clotting activity. Briefly, we propose two relatively distinctive functions of factor IX for two adjacent regions in the EGF-2 domain; the first loop region (residues 89 -94) is involved with the binding of its cofactor, factor VIIIa, and the third loop with connected ␤-sheets (residues 102-108) is involved in the proper binding to the substrate, factor X.

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Glycoprotein Folding in the Endoplasmic Reticulum

Cited by 14 publications

References 281 publications

Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus

Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus

The Secretion Pathway in Filamentous Fungi: A Biotechnological View

Identification of Functionally Important Residues of the Epidermal Growth Factor-2 Domain of Factor IX by Alanine-scanning Mutagenesis

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