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PMID: 2429970 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Assembly of influenza hemagglutinin trimers and its role in intracellular transport.

The Journal of cell biology ·Vol. 103 ·No. 4 ·1986-10-00 ·Pages 1179-91

Copeland CS, Doms RW, Bolzau EM, Webster RG, Helenius A

Abstract

The hemagglutinin (HA) of influenza virus is a homotrimeric integral membrane glycoprotein. It is cotranslationally inserted into the endoplasmic reticulum as a precursor called HA0 and transported to the cell surface via the Golgi complex. We have, in this study, investigated the kinetics and cellular location of the assembly reaction that results in HA0 trimerization. Three independent criteria were used for determining the formation of quaternary structure: the appearance of an epitope recognized by trimer-specific monoclonal antibodies; the acquisition of trypsin resistance, a characteristic of trimers; and the formation of stable complexes which cosedimented with the mature HA0 trimer (9S20,w) in sucrose gradients containing Triton X-100. The results showed that oligomer formation is a posttranslational event, occurring with a half time of approximately 7.5 min after completion of synthesis. Assembly occurs in the endoplasmic reticulum, followed almost immediately by transport to the Golgi complex. A stabilization event in trimer structure occurs when HA0 leaves the Golgi complex or reaches the plasma membrane. Approximately 10% of the newly synthesized HA0 formed aberrant trimers which were not transported from the endoplasmic reticulum to the Golgi complex or the plasma membrane. Taken together the results suggested that formation of correctly folded quaternary structure constitutes a key event regulating the transport of the protein out of the endoplasmic reticulum. Further changes in subunit interactions occur as the trimers move along the secretory pathway.

MeSH Terms
Animals Biological Transport Cell Line Cell Membrane/metabolism Chlorocebus aethiops Epitopes/immunology Fibroblasts/metabolism Golgi Apparatus/metabolism Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral/immunology,metabolism Influenza A virus/analysis Kidney Models, Molecular Protein Conformation Recombinant Proteins/immunology,metabolism Trypsin/pharmacology
Chemicals
Epitopes Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral Recombinant Proteins Trypsin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Copeland C S
Doms R W
Bolzau E M
Webster R G
Helenius A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.103.4.1179
Published
1986-10-00
Pages
1179-91
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2114319
Subset
IM
Grants
NIAID NIH HHS · AI-08831 · United States
NIAID NIH HHS · AI-18582 · United States
NIGMS NIH HHS · GM-07223 · United States
External Links
PubMed source DOI: 10.1083/jcb.103.4.1179 PMC Full Text View journal details
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