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

  title={A spring-loaded mechanism for the conformational change of influenza hemagglutinin},
  author={Chavela M. Carr and Peter S. Kim},

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Anatomy of the coiled coil and its role in the conformational change of influenza hemagglutinin
Evidence that the "native," fusioninactive conformation of HA is trapped in a metastable state, which, when destabilized, undergoes the conformational change and induces membrane fusion is described.
Membrane fusion mediated by coiled coils: a hypothesis.
Site-directed mutagenesis of the hinge peptide from the hemagglutinin protein: enhancement of the pH-responsive conformational change.
The conformational transition of a bacterially expressed LOOP-36 was found to be less dramatic than has been previously reported, and the substitution of the glycine residue at position 22 with alanine resulted in significant pH-responsive behavior.
New Insights into the Spring-Loaded Conformational Change of Influenza Virus Hemagglutinin
Six additional mutants are made with single proline substitutions in the region that undergoes the spring-loaded conformational change and two additional mutants with double proline substitution in this region are analyzed, supporting the hypothesis that theSpring- loaded conformationalchange is necessary for fusion.
Influenza hemagglutinin is spring-loaded by a metastable native conformation.
Results indicate that the native structure of HA is trapped in a metastable state and that the fusogenic conformation is released by destabilization of native structure, which could have implications for understanding the membrane-fusion step of HIV infection.
The impact of influenza hemagglutinin fusion peptide length and viral subtype on its structure and dynamics.
It is postulated that the closed state of the 20-residue peptide plays an essential role in the fusion process, and opening of this hairpin structure may be essential to the formation of a membrane pore at the final stage of the fusionprocess.
Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill
The results do not support a description of the B loop in group 2 HAs as a stiff spring, but, rather, it allows for more structural heterogeneity in the placement of the fusion peptides during the fusion process.
Order and disorder control the functional rearrangement of influenza hemagglutinin
This study reiterates the roles that cracking and disorder can play in functional molecular motions, in contrast to the downhill mechanical interpretations of the “spring-loaded” model proposed for the HA2 conformational transition.
Structural Characterization of an Early Fusion Intermediate of Influenza Virus Hemagglutinin †
This study reveals the possible initial structural event that leads to release of the B loop from its prefusion conformation, which is aided by unexpected structural changes within the membrane-distal HA1 domain at low pH.


Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution
The haemagglutinin glycoprotein of influenza virus is a trimer comprising two structurally distinct regions: a triple-stranded coiled-coil of α-helices extends 76 Å from the membrane and a globular
Intermonomer disulfide bonds impair the fusion activity of influenza virus hemagglutinin
It is shown that Cys-HA expressed on the cell surface is predominantly a disulfide-bonded trimer, which is impaired in its membrane fusion activity and its ability to change conformation at a low pH, as assessed by proteinase K sensitivity.
Membrane fusion activity of the influenza virus hemagglutinin. The low pH-induced conformational change.
Influenza virus haemagglutinin. Structural predictions suggest that the fibrillar appearance is due to the presence of a coiled-coil.
Predictions of secondary structure for the two chains HA1 and HA2 of the haemagglutinin from the Hong Kong influenza virus A/Memphis/102/72 reveal a striking contrast between the potential
The structure of a membrane fusion mutant of the influenza virus haemagglutinin.
The neutral pH crystal structure of one such mutant HAs from mutant viruses with raised fusion pH optima is determined, and it appears that four intra‐chain hydrogen bonds that stabilize the location of the N‐terminus of HA2 are lost in the mutant, resulting in a local destabilization that facilitates the extrusion of theN‐ terminus at higher pH.
Studies on the structure of the influenza virus haemagglutinin at the pH of membrane fusion.
Analysis of the structure of the soluble fragments and of HA in its low pH conformation showed that, although the membrane distal globular domains lose their trimer structure at the pH of fusion, the central fibrous stem of the molecule remains trimeric and assumes a more stable conformation.
Fusion mutants of the influenza virus hemagglutinin glycoprotein
Quaternary structure of influenza virus hemagglutinin after acid treatment
Negative-stain electron microscopy supported the notion that HA molecules in virus particles do not dissociate upon acidification and may form larger oligomeric structures in the plane of the viral membrane and the role of the transmembrane anchors of HA in preventing dissociation of the trimer.
A synthetic peptide inhibitor of human immunodeficiency virus replication: correlation between solution structure and viral inhibition.
The results suggest that both oligomerization and ordered structure are necessary for biological activity and provide insights into the role of this region in HIV infection and the potential for development of a new class of antiviral agents.
Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion.
  • J. Skehel, P. Bayley, D. Wiley
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1982
CD, electron microscopic, and sedimentation analyses show that bromelain-solubilized hemagglutinin (BHA) aggregates as protein-protein rosettes and acquires the ability to bind both lipid vesicles and nonionic detergent.