Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus
| Autor: | Kotecha, Abhay, Wang, Quan, Dong, Xianchi, Ilca, Serban L., Ondiviela, Marina, Zihe, Rao, Seago, Julian, Charleston, Bryan, Fry, Elizabeth E., Abrescia, Nicola G. A., Springer, Timothy A., Huiskonen, Juha T., Stuart, David I. |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Integrins
Binding Sites Science viruses Amino Acid Motifs Cryoelectron Microscopy CHO Cells biochemical phenomena metabolism and nutrition Virus Replication Article Capsid Cricetulus Antigens Neoplasm Foot-and-Mouth Disease Virus Polysaccharides Cricetinae Animals Receptors Virus Capsid Proteins Hydrophobic and Hydrophilic Interactions Oligopeptides Protein Binding |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-8 (2017) |
| ISSN: | 2041-1723 |
| Popis: | Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine–glycine–aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1. Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections. HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding. Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy. In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues. In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role. Foot-and-mouth disease virus binds αvβ6 integrin, via a conserved RGD motif in the flexible, exposed GH loop of capsid protein VP1, for cell entry. Here Kotecha et al. visualize this interaction with the VP1 GH loop extending away from the viral surface, engaging αvβ6 in an open, active state. |
| Databáze: | OpenAIRE |
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