Bacterial Mla intermembrane phospholipid transport

Phospholipid exchange between the outer and inner membranes of diderm (Gram-negative-type) bacteria by the Mla (maintenance of lipid asymmetry) system. Three interfaces are required: an outer-membrane MlaA/VacJ lipoprotein, which in characterized enterobacteria sits in a complex with trimeric porins and accesses phospholipid in the outer leaflet; a soluble periplasmic MlaC carrier that binds phospholipid in a hydrophobic pocket and shuttles it between the membranes; and the inner-membrane MlaFEDB ABC complex, in which the MlaE permease and the hexameric MCE-domain MlaD ring form a continuous lipid pathway energized by MlaF ATP hydrolysis, with the STAS-domain MlaB bound to MlaF on the cytoplasmic side. The system keeps phospholipid out of the lipopolysaccharide-rich outer leaflet; the module represents the conserved transport architecture without forcing a single retrograde or anterograde net direction.

Taxonomic scope. The Mla system is conserved across diderm Proteobacteria and beyond; every leaf is grounded with two exemplars from different orders: the experimentally defined Escherichia coli K-12 system (MlaA, MlaB, MlaC, MlaD, MlaE, MlaF; the genetic, biochemical and structural reference, and the PAINT seed for every PANTHER node used here) and the Pseudomonas putida KT2440 system (VacJ, Ttg2E, Ttg2D, MlaD, MlaE, MlaF), whose legacy toluene-tolerance names Ttg2D and Ttg2E correspond to the MlaC and MlaB roles by domain, orthology and contiguous operon context. The scope is deliberately bacterial. MlaE (PTHR30188:SF4) and MlaF (PTHR43023) families also contain the plant chloroplast TGD1 and TGD3 proteins, which with the MCE protein TGD2 move lipids from the ER into the plastid; that is a different organelle process and is not modeled here. Mycobacterial Mce/YrbE systems share MCE and permease folds but import lipids such as cholesterol and fatty acids across a different envelope. Those members sit inside the selected subfamilies, not merely in the parent families: PTHR30188:SF4 also holds YrbE1A and YrbE4A, PTHR43023:SF6 also holds Mkl/MceG, and PTHR33371:SF4 also holds Mce1D-Mce4D, so each family review scopes the phospholipid-specific terms with member exceptions for them. Shared MlaF/E/D-like domains alone therefore do not assign a protein to this module (P. putida PP_0140-PP_0142 are such a separate Mce-like system, and PP_1737 is a second MlaA-family protein without the canonical VacJ assignment; neither is counted as a duplicate core component). Transport direction is deliberately unresolved: reconstituted biochemistry favors ATP-driven retrograde (outer-to-inner membrane) transport, but anterograde models have been published and direction may vary with context. OmpC/OmpF are the characterized porin partners of E. coli MlaA rather than a universally required named porin in every lineage, so the porin is not modeled as a separate required part.