論文

査読有り
2007年8月

A likelihood-based index of protein-protein binding affinities with application to influenza HA escape from antibodies

MOLECULAR BIOLOGY AND EVOLUTION
  • Teruaki Watabe
  • ,
  • Hirohisa Kishino
  • ,
  • Leonardo de Oliveira Martins
  • ,
  • Yasuhiro Kitazoe

24
8
開始ページ
1627
終了ページ
1638
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/molbev/msm079
出版者・発行元
OXFORD UNIV PRESS

In many biological systems, proteins interact with other organic molecules to produce indispensable functions, in which molecular recognition phenomena are essential. Proteins have kept or gained their functions during molecular evolution. Their functions seem to be flexible, and a few amino acid substitutions sometimes cause drastic changes in function. In order to monitor and predict such drastic changes in the early stages in target populations, we need to identify patterns of structural changes during molecular evolution causing decreases or increases in the binding affinity of protein complexes. In previous work, we developed a likelihood-based index to quantify the degree to which a sequence fits a given structure. This index was named the sequence-structure fitness (SSF) and is calculated empirically based on amino acid preferences and pairwise interactions in the structural environment present in template structures. In the present work, we used the SSF to develop an index to measure the binding affinity of protein-protein complexes defined as the log likelihood ratio, contrasting the fitness of the sequences to the structure of the complex and that of the uncomplexed proteins. We applied the developed index to the complexes formed between influenza A hemagglutinin (HA) and four antibodies. The anti body-antigen binding region of HA is under strong selection pressure by the host immune system. Hence. examination of the long-term adaptation of HA to the four antibodies could reveal the strategy of the molecular evolution of HA. Two antibodies cover the HA receptor-binding region, while the other two bind away from the receptor-binding region. By focusing on branches with a significant decline in bindin ability, we could detect key amino acid replacements and investigate the mechanism via conditional probabilities. The contrast between the adaptations to the two types of antibodies suggests that the virus adapts to the immune system at the cost of structural change.

Web of Science ® 被引用回数 : 4

リンク情報
DOI
https://doi.org/10.1093/molbev/msm079
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000248848400011&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/molbev/msm079
  • ISSN : 0737-4038
  • Web of Science ID : WOS:000248848400011

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