Fig. 4. The hybrid β sheet between ORM1 and LCB2a stabilizes the ORM1 N terminus in an inhibitory conformation.

(A) A close-up view of the hybrid β sheet between the N termini of ORM1 and LCB2a. (B) Comparison of AtORM1 and hORMDL3. The hORMDL3 subunit in the previously resolved SPT-ORMDL3 complex structures (PDB 7K0M and 6M4O) is named hORMDL3 and hORMDL3^*, respectively. (C) The CoA head of the potential acyl-CoA substrate clashes with Met¹⁴ and Asn¹⁵ of ORM1 in the AtSPT-ORM1 structure. The potential acyl-CoA binding site was implied by the superimposition of the AtSPT-ORM1 structure and the S-CoA–bound hSPT-ORMDL3^* structure (PDB 7CQK). (D) SPT activity of the SPT-ORM1 variants with N-terminal deletion of LCB2a or ORM1. (E) Inhibition curves of the SPT-ORM1 variants with N-terminal deletion of LCB2a or ORM1 by C6-PhCer.