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TitleStructure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 5110, Year 2022
Publish dateAug 30, 2022
AuthorsYoann Saucereau / Thomas H Wilson / Matthew C K Tang / Martin C Moncrieffe / Steven W Hardwick / Dimitri Y Chirgadze / Sandro G Soares / Maria Jose Marcaida / Nicholas J Gay / Monique Gangloff /
PubMed AbstractAedes 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 ...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.
External linksNat Commun / PubMed:36042238 / PubMed Central
MethodsEM (single particle)
Resolution3.41 - 4.23 Å
Structure data

11982

7b1b

EMDB-11982, PDB-7b1b:
Cryo-EM of Aedes Aegypti Toll5A dimer bound to Spz1C
Method: EM (single particle) / Resolution: 4.23 Å

11983

7b1c

EMDB-11983, PDB-7b1c:
Cryo-EM of Aedes Aegypti Toll5A trimer bound to Spz1C
Method: EM (single particle) / Resolution: 3.74 Å

11984

7b1d

EMDB-11984, PDB-7b1d:
Cryo-EM of Aedes Aegypti Toll5A
Method: EM (single particle) / Resolution: 3.41 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • aedes aegypti (yellow fever mosquito)
KeywordsIMMUNE SYSTEM / Mosquito vector biology / Toll receptor / LRR / Cystine knot domain

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