The self-sufficient Aspergillus fumigatus Δ9-fatty acid desaturase SdeA requires a fused cytochrome b5 domain and hinge-dependent self-association for virulence

In Aspergillus fumigatus, SdeA requires its fused cytochrome b5 module acting in cis within a hinge-organized self-associated complex to support growth and virulence in Galleria mellonella.

• Why it matters: It was unknown whether the covalent Cytb5 linkage in self-sufficient fungal Δ9-desaturases is architecturally required, limiting identification of exploitable vulnerabilities for antifungal targeting.
• What they did: AlphaFold3 predicted a Cytb5 dimer enabling electron tunneling, and reciprocal co-immunoprecipitation showed full-length SdeA self-associates in vivo; deleting Cytb5, mutating its heme-coordinating histidines, or removing the 25-residue hinge abolished growth and virulence.
• The result: The hinge deletion abolished stable SdeA self-association, and a detached Cytb5-containing segment did not restore function, defining cis, hinge-dependent self-association as essential for catalytically competent virulence.