Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti
| Autor: | Yoann Saucereau, Tom H. Wilson, Matthew C. K. Tang, Martin C. Moncrieffe, Steven W. Hardwick, Dimitri Y. Chirgadze, Sandro G. Soares, Maria Jose Marcaida, Nick Gay, Monique Gangloff |
|---|---|
| Přispěvatelé: | Saucereau, Yoann [0000-0002-7175-2416], Tang, Matthew CK [0000-0003-0572-422X], Hardwick, Steven W [0000-0001-9246-1864], Chirgadze, Dimitri Y [0000-0001-9942-0993], Soares, Sandro G [0000-0001-7205-2510], Marcaida, Maria Jose [0000-0003-0663-5309], Gangloff, Monique [0000-0001-6131-0115], Apollo - University of Cambridge Repository |
| Rok vydání: | 2022 |
| Předmět: |
101
medicine.medical_treatment 631/535/1258/1259 receptor 631/250/2503 General Physics and Astronomy mechanism 631/250/262 Mosquito Vectors Biology ligand Ligands General Biochemistry Genetics and Molecular Biology 38/91 cytokine spatzle Downregulation and upregulation Aedes Gene duplication medicine 82/103 Animals Receptor Gene 631/250/262/2106/2108 cystine-knot protein drosophila-melanogaster Multidisciplinary Innate immune system 101/28 article General Chemistry Ligand (biochemistry) 96/21 140/58 Immunity Innate Cell biology Cytokine immune-response cryo-em Neofunctionalization recognition negative cooperativity Arboviruses |
| Popis: | Aedes aegypti can act as a vector for viral pathogens but the mechanism of viral resistance and evolving host-pathogen tolerance are poorly understood. Here the authors structurally characterise a duplicated pair of interacting Toll immunoreceptors and the cytokine ligand Spaetzle1C and show their dose-dependent function and mechanism of activation. Aedes aegypti has evolved to become an efficient vector for arboviruses but the mechanisms of host-pathogen tolerance are unknown. Immunoreceptor Toll and its ligand Spaetzle have undergone duplication which may allow neofunctionalization and adaptation. Here we present cryo-EM structures and biophysical characterisation of low affinity Toll5A complexes that display transient but specific interactions with Spaetzle1C, forming asymmetric complexes, with only one ligand clearly resolved. Loop structures of Spaetzle1C and Toll5A intercalate, temporarily bridging the receptor C-termini to promote signalling. By contrast unbound receptors form head-to-head homodimers that keep the juxtamembrane regions far apart in an inactive conformation. Interestingly the transcriptional signature of Spaetzle1C differs from other Spaetzle cytokines and controls genes involved in innate immunity, metabolism and tissue regeneration. Taken together our results explain how upregulation of Spaetzle1C in the midgut and Toll5A in the salivary gland shape the concomitant immune response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|