Conserved dimerization architecture in C‐type lectins from virus‐vector mosquitoes

C‐type lectins (CTLs) play key roles in immunity and microbial carbohydrate recognition. In the vector‐mosquito Aedes aegypti , the C‐type lectin domain‐single (CTLD‐S) family comprises 34 soluble CTLs whose members are implicated in flavivirus dissemination and microbial homeostasis, yet their organization remains uncharacterized. We combine X‐ray crystallography, small‐angle X‐ray scattering (SAXS), molecular dynamics, and machine learning‐based structure prediction to characterize CTLs in Aedes aegypti . We determined the crystal structures of four representative CTLD‐S proteins: mosGCTL‐1, ‐3, ‐6, and ‐20. All crystals featured an identical homodimer arrangement, positioning both carbohydrate‐binding sites on the same molecular face. Dimerization was confirmed in solution and AlphaFold predictions across the entire family indicated that dimer formation may be a unifying feature of CTLD‐S proteins. For one mosGCTL structure, paucimannose glycans bound at a Ca ²⁺ ‐dependent site, demonstrating bidentate binding through one dimer. Machine learning‐based predictions indicated hundreds of possible CTLD‐S heterodimers may be viable, with wide‐ranging implications for preferred glycan binding through one dimer. Our findings reveal a conserved dimeric arrangement among mosquito lectins that may underpin ligand recognition relevant to vector–pathogen interactions.