Partial reconstitution analyses indicate the phospholipids transfer functions of the ERMES complex between membranes Shin Kawano1 and Toshiya Endo1*, 1Faculty of Life Sciences, Kyoto Sangyo University, Japan *Corresponding Author
Membrane contact sites in eukaryotic cells were proposed to mediate lipid exchange between distinct organelle membranes. The ERMES (ER-Mitochondria Encounter Structure) complex, consisting of four core subunits (Mmm1, Mmm2/Mdm34, Mdm10, and Mdm12), forms one of such contact sites between the ER and mitochondrial outer membranes in yeast. Here, we determined the crystal structures of Mdm12 from a yeast Kluyveromyces lactis with and without bound phospholipid. The structure of Mdm12 showed the presence of a deep hydrophobic pocket for lipid binding, sequestering the acyl chains of the bound phospholipid molecule. Therefore Mdm12 (and its homolog, Mmm1) is clearly a phospholipid binding protein with little substrate specificities. However, this does not mean that Mdm12 (and Mmm1) can transfer lipids between membranes. Surprisingly, either purified Mdm12 or Mmm1s (the soluble domain of Mmm1) alone exhibited only a weak ability to extract lipids from or transfer lipids between liposomes in vitro. However, once they form a hetero-oligomeric complex, the Mmm1s-Mdm12 complex showed high lipid extraction/transfer activity between liposomes. Mutations in the lipid-binding pocket in Mdm12 and Mmm1s impaired the lipid transfer activities between liposomes and furthermore caused defective phosphatidylserine transport from the isolated ER to mitochondrial membranes via ERMES in vitro. These observations suggest that the Mmm1s-Mdm12 complex of ERMES functions as a minimal unit for the lipid transfer reaction between membranes.
Reference: Kawano et al., JCB (2017)
Funding: Japan Society of the Promotion of Science (JSPS), CREST Grant from the Japan Science and Technology Corporation (JST)
Credits: None available.
You must be logged in and own this product in order to post comments.