Conformational change in a viral glycoprotein during maturation due to disulfide bond disruption
The fusion glycoprotein of Newcastle disease virus is synthesized as an inactive precursor, F/sub 0/. During intracellular transport and maturation, F/sub 0/ undergoes a conformational change resulting from the loss of intramolecular disulfide bonds. F/sub 0/ is also cleaved to yield F/sub 1/, F/sub 2/, the active, membrane-fusion form of the protein. Two monoclonal antibodies were used to explore this conformational change and its relationship to cleavage. These antibodies failed to precipitate the pulse-labeled fusion protein but did precipitate the F/sub 0/ and the F/sub 1/, F/sub 2/ forms of the chase fusion protein. Use of the inhibitors carbonylcyanide m-chlorophenylhydrazone and monensin showed that the fusion protein acquired the ability to react with the monoclonal antibodies after it left the rough endoplasmic reticulum but before it left the medial Golgi membranes and before it was cleaved. The acquisition of antigenicity correlates with the disruption of intramolecular disulfide bonds during transit through the cell. This correlation was directly confirmed. The pulse-labeled fusion protein could be recognized by both monoclonal antibodies if the protein was first reduced. The formation and disruption of intramolecular disulfide bonds as a posttranslational modification of glycoproteins is discussed.
- Research Organization:
- Univ. of Massachusetts Medical School, Worcester
- OSTI ID:
- 5879180
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:4
- Country of Publication:
- United States
- Language:
- English
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GLUCOPROTEINS
CONFORMATIONAL CHANGES
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CHEMICAL BONDS
ENZYME IMMUNOASSAY
LABELLED COMPOUNDS
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MONOCLONAL ANTIBODIES
NEWCASTLE DISEASE
SULFUR 35
TRACER TECHNIQUES
VIRUSES
AMINO ACIDS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOHYDRATES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
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INFECTIOUS DISEASES
ISOTOPE APPLICATIONS
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LIPOTROPIC FACTORS
MICROORGANISMS
NUCLEI
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ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PARASITES
PROTEINS
RADIOISOTOPES
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550201* - Biochemistry- Tracer Techniques