7B1C

Cryo-EM of Aedes Aegypti Toll5A trimer bound to Spz1C

Summary for 7B1C

• Entry DOI: 10.2210/pdb7b1c/pdb
• EMDB information: 11982 11983 11984
• Descriptor: Toll-like receptor, AAEL013433-PA, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: mosquito vector biology, toll receptor, lrr, cystine knot domain, immune system
• Biological source: Aedes aegypti (yellow fever mosquito); More
• Total number of polymer chains: 5
• Total formula weight: 296177.19

Authors

Gangloff, M.,Hardwick, S.W.,Chirgadze, D.Y. (deposition date: 2020-11-24, release date: 2022-07-13, Last modification date: 2024-11-13)

Primary citation

Saucereau, Y.,Wilson, T.H.,Tang, M.C.K.,Moncrieffe, M.C.,Hardwick, S.W.,Chirgadze, D.Y.,Soares, S.G.,Marcaida, M.J.,Gay, N.J.,Gangloff, M.
Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti.
Nat Commun, 13:5110-5110, 2022

PubMed Abstract: 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.

PubMed: 36042238
DOI: 10.1038/s41467-022-32690-6

Experimental method

ELECTRON MICROSCOPY (3.74 Å)