Peptide Models of the Cytoplasmic Tail of Influenza A/H1N1 Virus Hemagglutinin Expand Understanding its pH-Dependent Modes of Interaction with Matrix Protein M1.

Publisher: Springer Country of Publication: Netherlands NLM ID: 101212092 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-8355 (Electronic) Linking ISSN: 15723887 NLM ISO Abbreviation: Protein J Subsets: MEDLINE

Publication: 2005- : Dordrecht : Springer
Original Publication: Dordrecht, The Netherlands ; New York : Kluwer Academic/Plenum, c2004-

Influenza A Virus, H1N1 Subtype* ; Influenza, Human* ; Influenza A virus*/metabolism; Humans ; Hemagglutinins ; Peptides/chemistry ; Hydrogen-Ion Concentration

Influenza A virus hemagglutinin (HA) is a major virus antigen. No cryo-electron microscopy or X-ray data can be obtained for the HA intraviral (cytoplasmic) domain (CT) post-translationally modified with long fatty acid residues bound to three highly conserved cysteines. We recently proposed a model of HA CT of Influenza A/H1N1 virus possessing an antiparallel beta structure based on the experimental secondary structure analysis of four 14-15 amino acid long synthetic peptides, corresponding to the HA CT sequence, with free or acetaminomethylated cysteines. To dispel doubts about possible non-specific "amyloid-like" aggregation of those synthetic peptides in phosphate buffer solution, we have determined the order of oligomers based on blue native gel electrophoresis, membrane filtration, fluorescence spectroscopy and molecular modeling approaches. We have found that unmodified peptides form only low molecular weight oligomers, while modified peptides form both oligomers of low order similar to those found for unmodified peptides and high order conglomerates, which however are not of beta-amyloid-like fold. This study confirms that the beta structure previously detected by circular dichroism spectroscopy analysis is more likely the result of intrinsic propensity of the HA CT amino acid sequence than the consequence of aggregation. The structures of low order oligomers of the synthetic peptides were used for in silico experiments on modeling of HA CT interactions with matrix protein M1 at physiological and acidic pH levels and revealed two different areas of binding. Finally, tripeptides capable of blocking interactions between HA CT and M1 were proposed.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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Keywords: Blue native gel electrophoresis; Cytoplasmic tail of hemagglutinin; M1 protein; Macromolecular docking; Tripeptides; Tryptophan fluorescence

0 (H1N1 virus hemagglutinin)
0 (Hemagglutinins)
0 (Peptides)

Date Created: 20230323 Date Completed: 20230719 Latest Revision: 20230719

20240829

PMC10034248

10.1007/s10930-023-10101-z

36952102