Structural basis of VLCFA chain-length determination by the KCS6-CER2 complex in plants

Abstract

Very-long-chain fatty acids (VLCFAs) govern plant adaptation and development in a chain length-dependent manner. The elongation of VLCFAs is mediated by 3-ketoacyl-coenzyme A synthase (KCS) and ECERIFERUM2 (CER2) family protein cofactors, but the structural basis and mechanistic principles underlying chain-length determination remain elusive. Here, we report cryo-electron microscopy structures of citrus KCS6-CER2 and KCS6-CER2-like1 complexes, unveiling a kinked elongation tunnel whose hydrophobicity and volume determine VLCFA chain length. KCS6 functions as a catalytic module elongating VLCFAs up to chain length of 28 carbons (C28). CER2 family proteins further extend the tunnel formed by the KCS6 subunit, thus elongating VLCFAs to chain lengths longer than C28. These findings provide a plant-specific structural framework for VLCFA chain-length modulation and lay a foundation for engineering VLCFA biosynthesis for the improvement of crop resilience and VLCFA industrial value.