N-linked glycans with similar location in the fusion protein head modulate paramyxovirus fusion. 2003

Veronika von Messling, and Roberto Cattaneo
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.

N-linked glycans not only orchestrate the folding and intracellular transport of viral glycoproteins but also modulate their function. We have characterized the three glycans attached to fusion (F) proteins of the morbilliviruses canine distemper virus and measles virus. The individual Morbillivirus glycans have similar functional properties: the glycan at position 68 is essential for protein transport, and those at positions 36 and 75 modulate fusion (numbering according to the Newcastle disease virus [NDV] F protein sequence). Based on the crystal structure of the NDV F protein, we then predicted the locations of the Morbillivirus glycans: the glycan at position 36 is located in the F protein head, and those at positions 68 and 75 are located near the neck-stalk interface. NDV position 36 is not occupied by a glycan; the only glycan in that F protein head also has a fusion control function and grows from residue 366, located only 6 A from residue 36. We then exchanged the glycan at position 36 with the glycan at position 366 and showed functional complementation. Thus, structural information about the F proteins of Paramyxoviridae coupled with functional analysis disclosed a location in the protein head into which fusion-modulating glycans independently evolved.

UI MeSH Term Description Entries
D008561 Membrane Fusion The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. Fusion, Membrane,Fusions, Membrane,Membrane Fusions
D009522 Newcastle disease virus The most well known avian paramyxovirus in the genus AVULAVIRUS and the cause of a highly infectious pneumoencephalitis in fowl. It is also reported to cause CONJUNCTIVITIS in humans. Transmission is by droplet inhalation or ingestion of contaminated water or food. Avian Paramyxovirus 1,Paramyxovirus 1, Avian
D011134 Polysaccharides Long chain polymeric CARBOHYDRATES composed of MONOSACCHARIDES linked by glycosidic bonds. Glycan,Glycans,Polysaccharide
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D004217 Distemper Virus, Canine A species of MORBILLIVIRUS causing distemper in dogs, wolves, foxes, raccoons, and ferrets. Pinnipeds have also been known to contract Canine distemper virus from contact with domestic dogs. Canine Distemper Virus,Canine Distemper Viruses,Distemper Viruses, Canine
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014709 Vero Cells A CELL LINE derived from the kidney of the African green (vervet) monkey, (CHLOROCEBUS AETHIOPS) used primarily in virus replication studies and plaque assays. Cell, Vero,Cells, Vero,Vero Cell
D014760 Viral Fusion Proteins Proteins, usually glycoproteins, found in the viral envelopes of a variety of viruses. They promote cell membrane fusion and thereby may function in the uptake of the virus by cells. Fusion Proteins, Viral,Viral Fusion Glycoproteins,F Protein (Sendai Virus),F Protein Measles Virus,F Protein Newcastle Disease Virus,F Protein SV,F-Glycoprotein SV,F1 Polypeptide (Paramyxovirus),Fusion Glycoprotein, Viral,Fusion VP1 Protein,Glycoprotein, Viral Fusion,Measles Fusion Protein,Mumps Virus Fusion Protein,Paramyxovirus Fusion Protein,Sendai Virus Fusion Protein,Viral Fusion-GP,Virus Fusion Proteins,Fusion Glycoproteins, Viral,Fusion Protein, Measles,Fusion Protein, Paramyxovirus,Fusion Proteins, Virus,Fusion-GP, Viral,Glycoproteins, Viral Fusion,Proteins, Virus Fusion,VP1 Protein, Fusion,Viral Fusion GP,Viral Fusion Glycoprotein

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