A soluble domain of the membrane-anchoring chain of influenza virus hemagglutinin (HA2) folds in Escherichia coli into the low-pH-induced conformation

Jue Chen, Stephen A. Wharton, Winfried Weissenhorn, Lesley J. Calder, Frederick M. Hughson, John J. Skehel, Don C. Wiley

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Abstract

The extensive refolding of the membrane-anchoring chain of hemagglutinin (HA) of influenza virus (termed HA2) in cellular endosomes, which initiates viral entry by membrane fusion, suggests that viral HA is metastable. HA2 polypeptide residues 38-175 expressed in Escherichia colt are reported here to fold in vivo into a soluble trimer. The structure appears to be the same as the low-pH-induced conformation of vital HA2 by α-helical content, thermodynamic stability, protease dissection, electron microscopy, and antibody binding. These results provide evidence that the structure of the low-pH-induced fold of viral HA2 (TBHA2) observed crystallographically is the lowest-energy-state fold of the HA2 polypeptide. They indicate that the HA2 conformation in viral HA before low pH activation of its fusion potential is metastable and suggest that removal of the receptor-binding chain (HA1) is enough to allow HA2 to adopt the stable state. Further, they provide direct evidence that law pH is not required to form the membrane- fusion conformation but acts to make this state kinetically accessible in viral HA.

Original languageEnglish (US)
Pages (from-to)12205-12209
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number26
DOIs
StatePublished - Dec 19 1995

All Science Journal Classification (ASJC) codes

  • General

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