Fig. 6: Model for lipid translocation by LetAB.
From: LetA defines a structurally distinct transporter family
Proposed model for lipid translocation and LetA conformational changes. (1) The pore of MCE ring 1 is open when bound to LetA. Closed (left; PDB 6V0C) and open LetB (right) states are shown. Whether LetA is constitutively bound to LetB is unclear, as indicated by the black arrows and question mark. (2) A phospholipid binds to the central cleft of LetA, representing Lipid 2 from molecular dynamics simulations. (3) LetA adopts an alternative state, revealing an amphipathic groove. The alternative state may resemble AlphaFold model 149. This conformation results in a steric clash with LetB, making it likely that some conformational rearrangements simultaneously occur in LetB. (4) Lipid traverses the groove, as observed in SMD simulations, and (5) arrives in the periplasmic pocket, where R63 of LetB dictates lipid orientation. (6) LetA probably reverts to the cryo-EM state, driving the phospholipid into the LetB tunnel. This transport process may be active or passive.
