Author: Qiao, Hui; Pelletier, Sandra L.; Hoffman, Lucas; Hacker, Jill; Armstrong, R. Todd; White, Judith M.
Title: Specific Single or Double Proline Substitutions in the “Spring-loaded” Coiled-Coil Region of the Influenza Hemagglutinin Impair or Abolish Membrane Fusion Activity Document date: 1998_6_15
ID: 78fjem8s_75
Snippet: Why has it appeared relatively easy to disrupt the fusion activity of retro-, paramyxo-, and coronavirus fusion proteins by introducing mutations into their (predicted) coiled-coil regions in contrast to our experience with HA? There are three trivial possibilities: The first is due to differences in the analyses performed. Whereas the prior studies have used syncytia formation or infectivity as assays for fusion, we have focused on initial membr.....
Document: Why has it appeared relatively easy to disrupt the fusion activity of retro-, paramyxo-, and coronavirus fusion proteins by introducing mutations into their (predicted) coiled-coil regions in contrast to our experience with HA? There are three trivial possibilities: The first is due to differences in the analyses performed. Whereas the prior studies have used syncytia formation or infectivity as assays for fusion, we have focused on initial membrane fusion events. The second is that in some of the prior studies, structural aberrations or deficiencies in cell surface expression of some mutant glycoproteins may not have been detected. The third is that single Pro (or other) substitutions at other positions within HA2 54-81 may have been more detrimental. Barring these trivial differences, a more substantive possibility is that the discrepancy reflects fundamental differences between the fusion mechanisms of the influenza HA vs. those of retro-, paramyxo-, and coronaviruses.
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