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Quantification of Multivalent Interactions between Sialic Acid and Influenza A Virus Spike Proteins by Single-Molecule Force Spectroscopy.
Cuellar-Camacho, Jose Luis; Bhatia, Sumati; Reiter-Scherer, Valentin; Lauster, Daniel; Liese, Susanne; Rabe, Jürgen P; Herrmann, Andreas; Haag, Rainer.
Afiliação
  • Cuellar-Camacho JL; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.
  • Bhatia S; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.
  • Reiter-Scherer V; Department of Physics & IRIS Adlershof, Humboldt-Universität zu Berlin, Newtonstraße 15, 12489 Berlin, Germany.
  • Lauster D; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.
  • Liese S; Institute for Biology & IRI Life Sciences, Humboldt-Universität zu Berlin, Invalidenstraße 42, 10115 Berlin, Germany.
  • Rabe JP; Department of Mathematics, University of Oslo, Moltke Moes vei 35, 1053 Oslo, Norway.
  • Herrmann A; Department of Physics & IRIS Adlershof, Humboldt-Universität zu Berlin, Newtonstraße 15, 12489 Berlin, Germany.
  • Haag R; Institute for Biology & IRI Life Sciences, Humboldt-Universität zu Berlin, Invalidenstraße 42, 10115 Berlin, Germany.
J Am Chem Soc ; 142(28): 12181-12192, 2020 07 15.
Article em En | MEDLINE | ID: mdl-32538085
ABSTRACT
Multivalency is a key principle in reinforcing reversible molecular interactions through the formation of multiple bonds. The influenza A virus deploys this strategy to bind strongly to cell surface receptors. We performed single-molecule force spectroscopy (SMFS) to investigate the rupture force required to break individual and multiple bonds formed between synthetic sialic acid (SA) receptors and the two principal spike proteins of the influenza A virus (H3N2) hemagglutinin (H3) and neuraminidase (N2). Kinetic parameters such as the rupture length (χß) and dissociation rate (koff) are extracted using the model by Friddle, De Yoreo, and Noy. We found that a monovalent SA receptor binds to N2 with a significantly higher bond lifetime (270 ms) compared to that for H3 (36 ms). By extending the single-bond rupture analysis to a multibond system of n protein-receptor pairs, we provide an unprecedented quantification of the mechanistic features of multivalency between H3 and N2 with SA receptors and show that the stability of the multivalent connection increases with the number of bonds from tens to hundreds of milliseconds. Association rates (kon) are also provided, and an estimation of the dissociation constants (KD) between the SA receptors to both proteins indicate a 17-fold higher binding affinity for the SA-N2 bond with respect to that of SA-H3. An optimal designed multivalent SA receptor showed a higher binding stability to the H3 protein of the influenza A virus than to the monovalent SA receptor. Our study emphasizes the influence of the scaffold on the presentation of receptors during multivalent binding.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Siálicos / Glicoproteína da Espícula de Coronavírus Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Siálicos / Glicoproteína da Espícula de Coronavírus Idioma: En Ano de publicação: 2020 Tipo de documento: Article