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A spring-loaded mechanism for the conformational change of influenza hemagglutinin

Cell. 1993 May 21;73(4):823-32. doi: 10.1016/0092-8674(93)90260-w.

Abstract

Influenza hemagglutinin (HA) undergoes a conformational change that induces viral fusion with the cellular membrane. The structure of HA in the fusogenic state is unknown. We have identified a sequence in HA that has a high propensity for forming a coiled coil. Surprisingly, this sequence corresponds to a loop region in the X-ray structure of native HA: the loop is followed by a three-stranded, coiled-coil stem. We find that a 36 residue peptide (LOOP-36), comprising the loop region and the first part of the stem, forms a three-stranded coiled coil. This coiled coil is extended and stabilized in a longer peptide, corresponding to LOOP-36 plus the residues of a preceding, short alpha helix. These findings lead to a model for the fusogenic conformation of HA: the coiled-coil stem of the native state extends, relocating the hydrophobic fusion peptide, by 100 A, toward the target membrane.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral / chemistry*
  • Hemagglutinins, Viral / metabolism
  • Hydrogen-Ion Concentration
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Viral Fusion Proteins / chemistry*
  • Viral Fusion Proteins / metabolism

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral
  • Viral Fusion Proteins