TY - JOUR
T1 - Folding, trimerization, and transport are sequential events in the biogenesis of influenza virus hemagglutinin
AU - Copeland, Constance S.
AU - Zimmer, Klaus Peter
AU - Wagner, Krystn R.
AU - Healey, Glenn A.
AU - Mellman, Ira
AU - Helenius, Ari
N1 - Funding Information:
We are grateful to Con Beckers, Bill Balch. and David Keller, whose as sistance was invaluable In carrying out thts study. We thank Anthony I aMantla for advtce with the morphometnc analysis. the Se&on of Neuroanatomy. Yale llnlverslty School ot Medlclne. for use of eqwp-merit, Helana Hoover-Lltty fcr assistance with cell culture, and Ann Curley-WhItehouse for photoyrdphlc serweb We also acknowiedge Judy Wt-llte for prowdlng the SP64 vector, Peter Waltei for the dog pancreas mlcrosoTes. Robert Webster for antibody 1114, and Mary-Jane Gethlng for plasmid pSVFXHA Mary-Jane Gething and Jonathan Yewdell kindly discussed unpublished data Stella Hurtley critlcally read !he rnanuscrlpt Supported by grants GM 38346 and Al 18599 to A H and GM 29765 to I M C S C was wpported by a Connecticut High Technology Graduate Fellowshtp. the DcJtsche Forschungsgemernschaft The costs of publication of this article payment of page charges This article marked “aduerhsen;en:” In accordance solely to Indicate this fact
PY - 1988/4/22
Y1 - 1988/4/22
N2 - Results from several systems indicate that correct protein folding and subunit assembly correlate with the transport of membrane and secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex Because the site of oligomer assembly and its precise relationship to intracellular transport remain unclear we have studied in detail the folding and trimerization of the influenza virus hemagglutinin (HAO) relative to its transport from ER to Golgi. Trimerization and transport were analyzed using several different methods including transport inhibitors, temperature blocks semi-intact cells, in vitro protein translocation, and immunocytochemistry. Taken together, the results clearly demonstrate that trimerization occurs at a point prior to exit from the ER. Before assembly, HAO monomers were extensively folded and possessed intramolecular disulfide bonds, but monomers were not transported to the cis Golgi compartment. Thus, hemagglutinin progresses through at least two intermediate state: before transport to the Golgi: highly folded monomers and trimers that have not yet left the ER.
AB - Results from several systems indicate that correct protein folding and subunit assembly correlate with the transport of membrane and secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex Because the site of oligomer assembly and its precise relationship to intracellular transport remain unclear we have studied in detail the folding and trimerization of the influenza virus hemagglutinin (HAO) relative to its transport from ER to Golgi. Trimerization and transport were analyzed using several different methods including transport inhibitors, temperature blocks semi-intact cells, in vitro protein translocation, and immunocytochemistry. Taken together, the results clearly demonstrate that trimerization occurs at a point prior to exit from the ER. Before assembly, HAO monomers were extensively folded and possessed intramolecular disulfide bonds, but monomers were not transported to the cis Golgi compartment. Thus, hemagglutinin progresses through at least two intermediate state: before transport to the Golgi: highly folded monomers and trimers that have not yet left the ER.
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U2 - 10.1016/0092-8674(88)90381-9
DO - 10.1016/0092-8674(88)90381-9
M3 - Article
C2 - 3359486
AN - SCOPUS:0024294338
SN - 0092-8674
VL - 53
SP - 197
EP - 209
JO - Cell
JF - Cell
IS - 2
ER -