title: Conformational aspects of the acid-induced fusion mechanism of influenza virus hemagglutinin. Circular dichroism and fluorescence studies.
abstract: Circular dichroism and tryptophan fluorescence spectroscopy have been used to investigate the structures of the influenza virus membrane glycoprotein hemagglutinin, acid-treated hemagglutinin, and fragments of hemagglutinin derived by proteolysis. The conformational change in hemagglutinin which occurs at the pH of membrane fusion (pH 5-6) was associated with a significant change of the environment of tyrosine residues, a change in the environment of tryptophan residues, but no changes in secondary structure. Tryptic digestion of the hemagglutinin in its low pH conformation which releases one of the subunit polypeptides (HA1) caused minimal changes in tyrosine and tryptophan environments but a small secondary structural change in HA1. The secondary structure of the remainder of the molecule (HA2) was very similar to that predicted from the known x-ray crystallographic structure of the native molecule. However, fluorescence spectroscopy indicated a tertiary change in structure in the coiled coil of alpha-helices which form the fibrous central stem of the molecule. These results are consistent with a conformational change required for membrane fusion which involves a decrease of HA1/HA1, HA1/HA2 interactions and changes in tertiary structure not accompanied by changes in secondary structure.
authors.affiliation: Division of Virology, National Institute for Medical Research, London, Great Britain.
authors.forename: S A
authors.initials: SA
authors.lastname: Wharton
authors.forename: R W
authors.initials: RW
authors.lastname: Ruigrok
authors.forename: S R
authors.initials: SR
authors.lastname: Martin
authors.forename: J J
authors.initials: JJ
authors.lastname: Skehel
authors.forename: P M
authors.initials: PM
authors.lastname: Bayley
authors.forename: W
authors.initials: W
authors.lastname: Weis
authors.forename: D C
authors.initials: DC
authors.lastname: Wiley
mesh_terms: D002942:Circular Dichroism; D005453:Fluorescence; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000378:metabolism*; D011487:Protein Conformation; D014760:Viral Fusion Proteins / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D006389:Hemagglutinins, Viral; D014760:Viral Fusion Proteins