[Accumulation of amino acid substitutions promotes irreversible structural changes in the hemagglutinin of human influenza AH3 virus during evolution].
During protein evolution the amino acid substitutions accumulate with time. However, the effect of accumulation of the amino acid substitutions to structural changes has not been estimated well. We will propose that the discordance of amino acid substitution on the HA protein of influenza A virus is useful for the assessment of structural changes during evolution. Discordance value can be obtained from the experimental data of tolerance or intolerance by introducing site directed mutagenesis at the homologous positions of two HA proteins holding the same amino acid residues. The value of discordance correlated to the number of amino acid differences among proteins. In the H3HA discordance rate was calculated to be 0.45% per one amino acid change. Furthermore, discordance of amino acid substitutions suggests that tolerable amino acid substitutions in different order have a probability of promoting irreversible divergence of the HA protein to different subtypes.
Nakajima
Katsuhisa
K
Department of Virology, Medical School, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizhuo-ku, Nagoya 467, Japan. nakajima@med.nagoya-cu.ac.jp
Nobusawa
Eri
E
Nakajima
Setsuko
S
D019943:Amino Acid Substitution; D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics; D016297:Mutagenesis, Site-Directed
D019267:Hemagglutinin Glycoproteins, Influenza Virus; C483468:hemagglutinin, human influenza A virus