Figure 7. Proposed molecular mechanism.
(A) CIDEA targets the LD through its C-term amphipathic helix and once diffused to the LD surface, it forms cis CIDEA complexes by interacting through the C-term (126–155) region. When two CIDEA-containing LDs make contact, trans interactions between CIDEA molecules in each droplet can be established, which will facilitate the docking of the LDs. Both the N-term and the C-term would contribute by dimerizing with their counterparts of the neighbour LD. This trans interaction will anchor the CIDEA complexes in the LD–LD contact site, promoting a local enrichment of CIDEA. The monolayers of the two LDs will be maintained at short distance by the CIDEA complex. The amphipathic helices, embedded in the hydrophobic region of the membrane, will interact with the cone-shaped PA, creating a local perturbation in the phospholipid barrier that will increase its permeability to TAG. (B) The docking of the amphipathic helix to the membrane could facilitate the integration of TAG molecules within the phospholipid hydrophobic tails. Although the helix will be stabilized with its cationic residues pointing outwards, it will interact with PA molecules in its vicinity, which could be pulled out of the monolayer by the helix molecular dynamics. This could create a transitory discontinuity in the polar barrier that will reduce the energy required to transfer the TAG molecules present in the membrane. This alteration, together with the microenvironment created by the CIDEA complex, will reduce the energy barrier necessary to transfer TAG molecules between LDs, allowing the LD growth by lipid transference.