Internal Lipid Architecture of the Hetero-Oligomeric Cytochrome b6f Complex

The role of lipids in the assembly, structure, and function of hetero-oligomeric membrane protein complexes is poorly understood. The dimeric photosynthetic cytochrome b(6)f complex, a 16-mer of eight distinct subunits and 26 transmembrane helices, catalyzes transmembrane proton-coupled electron transfer for energy storage. Using a 2.5 angstrom crystal structure of the dimeric complex, we identified 23 distinct lipid-binding sites per monomer. Annular lipids are proposed to provide a connection for super-complex formation with the photosystem-I reaction center and the LHCII kinase enzyme for transmembrane signaling. Internal lipids mediate crosslinking to stabilize the domain-swapped iron-sulfur protein subunit, dielectric heterogeneity within intermonomer and intramonomer electron transfer pathways, and dimer stabilization through lipid-mediated intermonomer interactions. This study provides a complete structure analysis of lipid-mediated functions in a multi-subunit membrane protein complex and reveals lipid sites at positions essential for assembly and function.