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

Area of Science:

• Plant Biology
• Biochemistry
• Structural Biology

Background:

• Very-long-chain fatty acids (VLCFAs) are essential lipids regulating plant adaptation and development.
• The biosynthesis and precise chain-length determination of VLCFAs involve 3-ketoacyl-coenzyme A synthase (KCS) and ECERIFERUM2 (CER2) proteins.
• The structural and mechanistic basis for VLCFA chain-length control remains largely unknown.

Purpose of the Study:

• To elucidate the structural basis of VLCFA chain-length determination in plants.
• To understand the mechanistic roles of KCS and CER2 family proteins in modulating VLCFA elongation.
• To provide a structural framework for engineering VLCFA biosynthesis.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to determine the structures of citrus KCS6-CER2 and KCS6-CER2-like1 complexes.
• Structural analysis focused on the elongation tunnel and its properties influencing chain length.

Main Results:

• Cryo-EM structures revealed a kinked elongation tunnel within the KCS6-CER2 complexes.
• The tunnel's hydrophobicity and volume dictate the final VLCFA chain length.
• KCS6 elongates VLCFAs up to C28, while CER2 proteins extend the tunnel for longer chain production (>C28).

Conclusions:

• The study provides the first plant-specific structural insights into VLCFA chain-length modulation.
• The KCS-CER2 complex architecture explains how different VLCFA chain lengths are achieved.
• Findings offer a foundation for improving crop resilience and industrial applications of VLCFAs through metabolic engineering.