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PMID: 8790377 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Effects of inefficient cleavage of the signal sequence of HIV-1 gp 120 on its association with calnexin, folding, and intracellular transport.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 18 ·1996-09-03 ·Pages 9606-11

Li Y, Bergeron JJ, Luo L, Ou WJ, Thomas DY, Kang CY

Abstract

The HIV-1 envelope glycoprotein gp120 displays inefficient intracellular transport, which is caused by its retention in the endoplasmic reticulum. Coexpression in insect cells (Sf9) of HIV-1 gp120 with calnexin has shown that their interaction was modulated by the signal sequence of HIV-1 gp120. gp120, with its natural signal sequence, showed a prolonged association with calnexin with a t1/2 of greater than 20 min. Replacement of the natural signal sequence with the signal sequence from mellitin led to a decreased time of association of gp120 with calnexin (t1/2 < 10 min). These different times of calnexin association coincided both with the folding of gp120 as measured by the ability of bind CD4 and with endoplasmic reticulum to Golgi transport as analyzed by the acquisition of partial endoglycosidase H resistance. Using a monospecific antibody to the HIV-1 gp120 natural signal peptide, we showed that calnexin associated with N-glycosylated but uncleaved gp120. Only after dissociation from calnexin was gp120 cleaved, but very inefficiently. Only the small proportion of signal-cleaved gp120 molecules acquired transport competence and were secreted. This is the first report demonstrating the effect of the signal sequence on calnexin association.

MeSH Terms
Animals Biological Transport CD4 Antigens/metabolism Calcium-Binding Proteins/metabolism Calnexin Electrophoresis, Polyacrylamide Gel Endoplasmic Reticulum/metabolism Glycosylation HIV Envelope Protein gp120/metabolism HIV-1/metabolism Hexosaminidases/metabolism Melitten/metabolism Protein Folding Protein Sorting Signals/metabolism Spodoptera
Chemicals
CD4 Antigens Calcium-Binding Proteins HIV Envelope Protein gp120 Protein Sorting Signals Calnexin Melitten Hexosaminidases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Li Y
Department of Zoology, Faculty of Science, University of Western Ontario, London, Canada.
Bergeron J J
Luo L
Ou W J
Thomas D Y
Kang C Y
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.18.9606
Published
1996-09-03
Pages
9606-11
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38475
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.18.9606 PMC Full Text View journal details
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