Background: All cells rely on lipids for key functions. Lipid transfer proteins allow lipids to exit the hydrophobic environment of bilayers, and cross aqueous spaces. One lipid transfer domain fold present in almost all eukaryotes is the TUbular LIPid binding (TULIP) domain. Three TULIP families have been identified in bacteria (P47, OrfX2 and YceB), but their homology to eukaryotic proteins is too low to specify a common origin. Another recently described eukaryotic lipid transfer domain in VPS13 and ATG2 is Chorein-N, which has no known bacterial homologues. There has been no systematic search for bacterial TULIPs or Chorein-N domains.
Results: Remote homology predictions for bacterial TULIP domains using HHsearch identified four new TULIP domains in three bacterial families. DUF4403 is a full length pseudo-dimeric TULIP with a 6 strand β-meander dimer interface like eukaryotic TULIPs. A similar sheet is also present in YceB, suggesting it homo-dimerizes. TULIP domains were also found in DUF2140 and in the C-terminus DUF2993. Remote homology predictions for bacterial Chorein-N domains identified strong hits in the N-termini of AsmA and TamB in diderm bacteria, which are related to Mdm31p in eukaryotic mitochondria. The N-terminus of DUF2993 has a Chorein-N domain adjacent to its TULIP domain.
Conclusions: TULIP lipid transfer domains are widespread in bacteria. Chorein-N domains are also found in bacteria, at the N-terminus of multiple proteins in the intermembrane space of diderms (AsmA, TamB and their relatives) and in Mdm31p, a protein that is likely to have evolved from an AsmA/TamB-like protein in the endosymbiotic mitochondrial ancestor. This indicates that both TULIP and Chorein-N lipid transfer domains may have originated in bacteria.
Keywords: AsmA; Chorein-N domain; HHpred; Lipid transfer protein; Mdm31p; Translocation and assembly module-B (TamB); Tubular lipid binding domain (TULIP); VPS13.